ApoE

  1. Liu CCI, Kanekiyo T, Xu H, Bu G. Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nat Rev Neurol.  2013 Feb 9 (2):106-18.  Doi: 10.1038/nrneurol. 2012.263.
  2. Shankar GM, Li S Mehta TH, Garcia-Munoz A., Shepardson NE, Smith I, Brett FM, Farrell MA, Rowan MJ, Lemere CA Regan CM, Walsh DM, Sabatinis BL, Selkoe DJ (Aug 2008). “Amyloid-beta protein dimers isolated directly from Alzheimer’s brains impair synaptic plasticity and memory”. Nature Medicine. 14 (8): 837-42. dol:10.1038/nm1782.
  3. Prelli F, Castario E., Glenner GG, Frangione B (Aug 1988). “Differences between vascular and plaque core amyloid in Alzheimer’s disease”.  Journal of Neurochemistry.  51 (2):648-51.  Doi:10.1111/j.1471-4159.1988.tb01087.x.
  4. Harold, D. et al. Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer’s disease. Nat. Genet. 41, 1088-1093 (2009).
  5. Lambert, J.C. et al Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer’s disease.   Genet.41, 1094-1099 (2009).

Cardiac Health

  1. Roberts R and Stewart A. 9p21 and the genetic Revolution for Coronary Artery Disease. Clinical Chemistry. 2012; 58(1):104-112.
  2. Catt KJ et al. Angiotensin II blood levels in human hypertension. The Lancet. 1971; 297:459-464.
  3. Wang WZ. Association between T174M polymorphism in the angiotensinogen gene and risk of coronary artery disease: a meta-analysis. J Geriatr Cardiol. 2013: 10:59-65.
  4. Cosentino F and Luscher TF. Maintenance of vascular integrity: role of nitric oxide and other bradykinin mediators. Eur Heart J. 1995; 16 Suppl K:4-12.
  5. Tesauro M et. Al. Intracellular processing of endothelial nitric oxide synthase isoforms associated with differences in severity of cardiopulmonary diseases: cleavage of proteins with aspartate vs. glutamate at position 298. Proc Natl Acad Sci USA. 2006:2832-2835.
  6. Wang M et al. Association of G894T polymorphism in endothelial nitric oxide synthase gene with the risk of ischemic stroke: A meta-analysis.Biomed Rep. 2013: (1)1:144-150.
  7. Refsum H et al. The Hordaland Homocysteine Study: A community-Based Study of Homocysteine, Its Determinants, and Associations with Disease. J Nutr. 2006; 136:1731S-174OS.
  8. Frost P et. Al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet.1995; 10-111-113.
  9. Cotlarciuc I et al. Effect of genetic variants associated with plasma homocysteine levels on stroke risk. Stroke. 2014; 45(7):1920-4.
  10. Weisberg I et al. A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Mol Genet Metab. 1998; 64:169-72
  11. Poort SR et.al. A common genetic variation in the 3’-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood. Nov 15, 1996:88(10):3698-703.
  12. Simone B et al. Risk of venous thromboembolism associated with single and combined effects of Factor V Leiden, Prothrombin 20210A and Methylenetethraydrofolate reductase C677T: a meta-analysis involving over 11,000 cases and 21,000 controls. Eur J Epidemiol. 2013; 28(8):621-47.
  13. Gohil, R et al. The Genetics of Venous Thromboembolism: A meta-analysis involving 120,000 cases and 180,000 controls. Journal of Thrombosis and Haemostasis. 2009; 102: 360-370.
  14. Kujovich J et. al GeneReviews; 1999 “Factor V Leiden Thrombophilia”.
  15. Bertina RM et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature. 1994; 369(6475):64-7.
  16. Mahley RW et al. Apolipoprotein E: Far More Than a Lipid Transport Protein. Annu Rev Genomics Hum Genet. 2000; 1:507-537.
  17. Howard BV et al. Association of Apolipoprotein E Phenotype with Plasma lipoproteins in African-American and White Young Adults. Am J Epidemiol. 1998: 148(9):859-868.
  18. Niemi M et al. Organic Anion Transporting Protein 181:a Genetically Polymorphic Transporter of Major Importance for Hepatic Drug Uptake. Pharm Review. 2011; 63(1): 157-181.
  19. Saita E et al. Anti-inflammatory Diet for Atherosclerosis and Coronary Artery Disease: Antioxidant Foods. Clinical Medicine Insights: Cardiology. 2014:8(S3) 61-65.
  20. Fan E, Zhang L, Jiang S, Bai Y. Beneficial effects of resveratrol on atherosclerosis. J Med Food. 2008;11(4):610-4.
  21. Hosogoe N et al. Add-on Antiplatelet Effects of Eicosapentaenoic Acid with Tailored Dose Setting in Patients on Dual Antiplatelet Therapy. Int Heart J. 2017 Ag 3; 58 (4): 481-485.
  22. Ho, H. T. et al. A systematic review and meta-analysis of randomized controlled trials of the effect of konjac glucomannan, a viscous soluble fiber, on LDL cholesterol and the new lipid targets non-HDL cholesterol and apolipoprotein B. Am J Clin Nutr. 2017; 105(5):1239-1247.
  23. Zelman, K. April 07, 2016. Fiber: How Much Do I Need? WebMD. https://www.webmd.com/diet/guide/fiber-how-much-do-you-need#1. [2017,October 2]
  24. Nordmann A et al. Effects of Low-Carbohydrate vs Low-fat Diets on Weight loss and Cardiovascular Risk Factors. Arch Intern Med. 2006; 166:285-293.

Celiac – DQ2/DQ8

  1. Megiorni F et al. HLA-DQ and risk gradient for celiac disease. Hum Imm. 2009; 70:55-59.
  2. Megiorni F et al. HLA-DQA1 and HLA-DQB1 in celiac disease predisposition: practical implications of the HLA molecular typing. J of Biomed Sci. 2012; 19:88.
  3. Abadie et al. Integration of genetic and immunological insights into a model of celiac disease pathogenesis. Annu. Rev. Immunol. 2011; 29:493-525.
  4. Kagnoff MF. Celiac disease: pathogenesis of a model immunogenetic disease. J Clin Invest. 2007; 117:41-49.
  5. Megiorni F et al. HLA-DQ and susceptibility to celiac disease: evidence for gender differences and parent-of-origin effects. Am J Gastroenterol. 2008; 103:997-1003.
  6. Karell et al. HLA types in celiac disease patients not carrying the DQA1*05-DQB1*02(DQ2) heterodimer: results from the European genetics cluster of celiac disease. Hum Immunol. 2003; 64:469-477

Comprehensive Genetic

  1. Jalba MS, Rhoads GG, Demissie K. Association of codon 16 and codon 27 beta 2-adrenergic receptor gene polymorphisms with obesity: a meta-analysis. Obesity (Silver Spring). 2008;16(9):2096-106.
  2. Lange LA, Norris JM, Langefeld CD, et al. Association of adipose tissue deposition and beta-2 adrenergic receptor variants: the IRAS family study. Int J Obes (Lond). 2005;29(5):449-57.
  3. Martínez JA et al. Obesity risk is associated with carbohydrate intake in women with the Gln27Glu β2-adrenoreceptor polymorphism. J Nutr. 2003; 133:2549-2554.
  4. Large V et al. Human Beta-2 adrenoreceptor gene polymorphisms are highly frequent in obesity and associate with altered adipocyte Beta-2 adrenoceptor function. J Clin Invest. 1997; 100:3005-3013.
  5. Macho-Azcarate et al. Gln27Glu polymorphism in the beta2 adrenergic receptor gene and lipid metabolism during exercise in obese women. Int J Obesity. 2002; 26:1434-1441.
  6. HGNC. http://www.genenames.org/cgibin/gene_symbol_report? hgnc_id=HGNC:286.
  7. org. Nutrition and Healthy Eating: Carbohydrates: How carbs fit into a healthy diet. http://www.mayoclinic.org/healthy-living/nutrition-and-healthy-eating/in-depth/carbohydrates/art-20045705?pg=1.
  8. Layman DK. Dietary Guidelines should reflect new understandings about adult protein needs. Nutr Metab (Lond). 2009; 6:12.
  9. Phares DA et al. Association Between Body Fat Response to Exercise Training and Multilocus ADR Genotypes. Obes Res. 2004; 12(5):807-815.
  10. Corbalan MS et al. The 27Glu polymorphism of the Beta2-adrenergic receptor gene interacts with physical activity influencing obesity risk among female subjects. Clin Genet. 2002; 61:305-307.
  11. Zhang et al. Association of Gln27Glu and Arg16Gly Polymorphisms in Beta2-Adrenergic Receptor Gene with Obesity Susceptibility: A Meta-Analysis. PLoS ONE. 2014; 9(6): e100489.
  12. Martinez-lopez E, Garcia-garcia MR, Gonzalez-avalos JM, et al. Effect of Ala54Thr polymorphism of FABP2 on anthropometric and biochemical variables in response to a moderate-fat diet. Nutrition. 2013;29(1):46-51.
  13. Pratley RE, Baier L, Pan DA, et al. Effects of an Ala54Thr polymorphism in the intestinal fatty acid-binding protein on responses to dietary fat in humans. J Lipid Res. 2000;41(12):2002-8.
  14. Levy E et al. The polymorphism at codon 54 of the FABP2 gene increases fat absorption in human intestinal explants. J Biol Chem. 2001; 276:39679-39684.
  15. Marin C et al. The Ala54Thr polymorphism of the fatty acid-binding protein 2 gene is associated with a change in insulin sensitivity after a change in the type of dietary fat. Am J Clin Nutr. 2005; 82:196-200.
  16. Albala C et al. FABP2 Ala54Thr polymorphism and diabetes in Chilean elders. Diab Res Clin Pract. 2007; 77:245-250.
  17. Paglialunga S et al. Regulation of postprandial lipemia: an update on current trends. Appl Physiol Nutr Metab. 2007; 32:61-75.
  18. Takakura Y et al. Thr54 allele of the FABP2 gene affects resting metabolic rate and visceral obesity. Diabetes Res Clin Pract. 2005; 67:36-42.
  19. Hegele RA. A Review of Intestinal Fatty Acid Binding Protein Gene Variation and the Plasma Lipoprotein Response to Dietary Components. Clin Biochem. 1998; 31:609-612.
  20. Gaggini M et al. Non-Alcoholic Fatty Liver Disease (NAFLD) and Its Connection with Insulin Resistance, Dyslipidemia, Atherosclerosis and Coronary Heart Disease. Nutrients. 2013; 5:1544-1560.
  21. Almeida JC et al. The Ala54Thr polymorphism of the FABP2 gene influences the postprandial fatty acids in patients with type 2 diabetes. J Clin Endocrin Met. 2010; 95:3909-3917.
  22. Dworatzek PD et al. Postprandial lipemia in subjects with the threonine 54 variant of the fatty acid-binding protein 2 gene is dependent on the type of fat ingested. Am J Clin Nutr. 2004; 79:1110-1117.
  23. Weiss EP et al. FABP2 Ala54Thr genotype is associated with glucoregulatory function and lipid oxidation after a high-fat meal in sedentary nondiabetic men and women. Am J Clin Nutr. 2007; 85:102-108.
  24. Weickert MO et al. Metabolic Effects of Dietary Fiber consumption and Prevention of Diabetes. J Nutr. 2008; 138(3):439-442.
  25. org. Nutrition and Healthy Eating: Carbohydrates: How carbs fit into a healthy diet. http://www.mayoclinic.org/ healthy-living/nutrition-and-healthy-eating/in-depth/carbohydrates/ art-20045705?pg=1
  26. Pfeiffer M et al. The influence of walking performed immediately before meals with moderate fat content on postprandial lipemia. Lipids Health Dis. 2005; 4:24.
  27. Brandou F et al. Impact of high- and low-intensity targeted exercise training on the type of substrate utilization in obese boys submitted to a hypocaloric diet. Diabetes Metab. 2005; 31(4 Pt 1):327-325.
  28. Corella D et al. A High Intake of Saturated Fatty Acids Strengthens the Association between the Fat Mass and Obesity-Associated Gene and BMI. J of Nutr. 2011; 141:2219-2225.
  29. Kilpelainen TO et al. Physical Activity Attenuates the Influence of FTO Variants on Obesity Risk: A Meta-Analysis of 218,166 Adults and 19.268 Children. PLOS Medicine. 2011; 8(11):31001116.
  30. Frayling TM et al. A Common Variant in the FTO Gene is Associated with Body Mass Index and Predisposition to Childhood and Adult Obesity. Science. 2007; 316(58):889-894.
  31. Berulava T and Horsthemke B. The obesity-associated SNPs in intron 1 of the FTO gene affect primary transcript levels. Eur J Hum Genet. 2010; 18(9):1054-1058.
  32. Karra E et al. A link between FTO, ghrelin, and impaired brain food-cue responsivity. J Clin Invest. 2013; 123(8):3539-3551.
  33. Lu Y et al. Obesity genomics: assessing the transferability of susceptibility loci across diverse populations. Genome Med. 2013; 5:55.
  34. Cho YS et al. A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits. Nat Genet. 2009; 41:527-534.
  35. Jaaskelainen A et al. Meal Frequencies Modify the Effect of Common Genetic Variants on Body Mass Index in Adolescents of the Northern Finland Birth Cohort 1986. PLOS One. 2013; 8(9):e73802.
  36. Zhang X et al. FTO Genotype and 2-Year Change in Body Composition and Fat Distribution in Response to Weight-Loss Diets: The POUNDS Lost Trial. Diabetes. 2012; 61:3005-3011.
  37. Ortega-Azorin C et al. Associations of the FTO rs9939609 and the MC4R rs17782313 polymorphisms with type 2 diabetes are modulated by diet, being higher when adherence to the Mediterranean diet pattern is low. Cardiovasc Diabetol. 2012; 11:137.
  38. Mitchell JA et al. FTO Genotype and the Weight Loss Benefits of Moderate Intensity Exercise. Obesity. 2010; 18(3):641-643.
  39. Lauria F et al. Prospective Analysis of the Association of a Common Variant of FTO (rs9939609) with Adiposity in Children: Results of the IDEFICS Study. PLoS One. 2012; 7: e48876.
  40. Velders FP et al. FTO at rs9939609, food responsiveness, emotional control and symptoms of ADHD in preschool children. PLoS One. 2012; 7:e49131.
  41. Wardle J et al. Obesity associated genetic variation in FTO is associated with diminished satiety. J Clin Endocrinol Metab. 2008; 93:3640–3643.
  42. den Hoed M et al. Postprandial responses in hunger and satiety are associated with the rs9939609 single nucleotide polymorphism in FTO. Am J Clin Nutr. 2009; 90:1426–1432.
  43. Loos RJF et al. Common variants near MC4R are associated with fat mass, weight and risk of obesity. Nat Genet. 2008; 40(6):768-775.
  44. Qi L et al. The common obesity variant near MC4R gene is associated with higher intakes of total energy and dietary fat, weight change and diabetes risk in women. Human Mol Genetics 2008; 17:3502-3508.
  45. Xi B et al. Common polymorphism near the MC4R gene is associated with type 2 diabetes: data from a meta-analysis of 123,373 individuals. Diabetologia 2012; 55:2660–2666.
  46. Stutzmann F et al. Common genetic variation near MC4R is associated with eating behaviour patterns in European populations. Int J Obes. 2009; 33:373-378.
  47. Xi B et al. Influence of physical inactivity on associations between single nucleotide polymorphisms and genetic predisposition to childhood obesity. Am J Epidemiology 2011; 173:1256-1262.
  48. Acosta A et al. Association of melanocortin 4 receptor gene variation with satiation and gastric emptying in overweight and obese adults. Genes Nutr. 2014; 9(2):384.
  49. Zlatohlavek L et al. FTO and MC4R gene variants determine BMI changes in children after intensive lifestyle intervention. Clin Biochem. 2013; 46:313-31.
  50. Raynor HA et al. Dietary energy density and successful weight loss maintenance. Eat Behav. 2011; 12(2):119-125.
  51. Otten JJ et al. DRI: Dietary Reference Intakes: The Essential Guide to Nutrient Requirements. Washington, DC. National Academies Press. c2006.
  52. OSU: Linus Pauling Institute. Glycemic Index and Glycemic Load. http://lpi.oregonstate.edu/infocenter/foods/grains/gigl.html
  53. Jaaskelainen A et al. Meal Frequencies Modify the Effect of Common Genetic Variants on Body Mass Index in Adolescents of the Northern Finland Birth Cohort 1986. PLOS One. 2013; 8(9):e73802.
  54. Little JP et al. A practical model of low-volume high-intensity interval training induces mitochondrial biogenesis in human skeletal muscle: potential mechanisms. J Physiol. 2010; 588 (Pt 6):1011-1022.
  55. Bauer F et al. Obesity genes identified in genome-wide association studies are associated with adiposity measures and potentially with nutrient-specific food preference. Am J Clin Nutr. 2009; 90:951–959.
  56. Volckmar AL et al. Mutation screen in the GWAS derived obesity gene SH2B1 including functional analyses of detected variants. BMC Med Genomics. 2012; 5:65.
  57. Jamshidi Y et al. The SH2B gene is associated with serum leptin and body fat in normal female twins. Obesity. 2007; 15:5-9.
  58. Ren D et al. Neuronal SH2B1 is essential for controlling energy and glucose homeostasis. J Clin Invest. 2007; 117:397–406.
  59. Morris DL et al. SH2B1 enhances insulin sensitivity by both stimulating the insulin receptor and inhibiting tyrosine dephosphorylation of insulin receptor substrate proteins. Diabetes. 2009; 58:2039-2047.
  60. McCaffery JM et al. Obesity susceptibility loci and dietary intake in the Look AHEAD Trial. Am J Clin Nutr. 2012; 95:1477-1486.
  61. Duan C et al. Disruption of the SH2-B gene causes age-dependent insulin resistance and glucose intolerance. Mol Cell Biol 2004; 24:7435–7443.
  62. Ren D et al. Identification of SH2-B as a key regulator of leptin sensitivity, energy balance, and body weight in mice. Cell Metabolism. 2005; 2:95–104.
  63. Wolpert HA et al. Dietary Fat Acutely Increases Glucose Concentrations and Insulin Requirements in Patients With Type 1 Diabetes: Implications for carbohydrate-based bolus dose calculation and intensive diabetes management. Diabetes Care. 2012; 36(4):810-816.
  64. Diabetes.org American Diabetes Association: Insulin Basics. http://www.diabetes.org/living-with-diabetes/treatment-and-care/ medication/insulin/insulin-basics.html.
  65. Klok MD et al. The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review. Obes Rev. 2007; 8(1):21-34.
  66. Bachman JL et al. Eating frequency is higher in weight loss maintainers and normal-weight individuals than in overweight individuals. J Am Diet Assoc. 2011; 111(11):1730-4.
  67. Lichtenstein MB et al. Exercise Addiction in Men Is Associated With Lower Fat-Adjusted Leptin Levels. Clin J Sport Med. 2015; 25(2):138-43.
  68. OSU: Linus Pauling Institute. Glycemic Index and Glycemic Load. http://lpi.oregonstate.edu/infocenter/foods/grains/gigl.html
  69. Zhang Z et al. A high-legume low-glycemic index diet reduces fasting plasma leptin in middle-aged insulin-resistant and –sensitive men. Eur J Clin Nutr. 2011; 65(3):415-418.
  70. Fall T et al. The role of obesity-related genetic loci in insulin sensitivity. Diabet Med. 2012; 29(7):e62-66.
  71. Robiou-du-Pont S et al. Contribution of 24 obesity-associated genetic variants to insulin resistance, pancreatic beta-cell function and type 2 diabetes. Int J Obesity. 2013; 37:980-985.
  72. Weickert MO et al. Metabolic Effects of Dietary Fiber Consumption and Prevention of Diabetes. J Nutr. 2008; 138(3):439-442.
  73. Willett WC. Eat, Drink, and be Healthy: The Harvard Medical School Guide to Healthy Eating. New York: Simon & Schuster; 2001.
  74. Zaccaria M et al. Plasma leptin and energy expenditure during prolonged, moderate intensity, treadmill exercise. J Endocrinol Invest. 2013; 36(6):396-401.
  75. Li S et al. Physical Activity Attenuates the Genetic Predisposition to Obesity in 20,000 Men and Women from EPIC-Norfolk Prospective Population Study. PLOS Medicine. 2010; 7(8):e1000332.
  76. Lee S et al. Aerobic exercise but not resistance exercise reduces intrahepatic lipid content and visceral fat and improves insulin sensitivity in obese adolescent girls: a randomized controlled trial. Am J Physiol Endocrinol Metab. 2013; 305(10):E1222-1229.
  77. Karvanen J, Silander K, Kee F, et al. The impact of newly identified loci on coronary heart disease, stroke and total mortality in the MORGAM prospective cohorts. Genet Epidemiol. 2009;33(3):237-46.
  78. Ye S et al. Association of Genetic Variation on Chromosome 9p21 with Susceptibility and Progression of Atherosclerosis. JACC 2008; 52(5): 378-384.
  79. Roberts R. Genetics of Coronary Artery Disease. Circ Res. 2014; 114:1890-1903.
  80. The Wellcome Trust Case Consortium, Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature. 2007; 447(7145): 661-678.
  81. Genetics Home Reference. Genes: CDKN2A, http://ghr.nlm.nih.gov/gene/CDKN2A 4.
  82. Roberts R and Stewart A. 9p21 and the Genetic Revolution for Coronary Artery Disease. Clinical Chemistry. 2012; 58(1):104-112.
  83. Munir M et al. The association of 9p21-3 locus with coronary atherosclerosis: a systematic review and meta-analysis. BMC Medical Genetics. 2014; 15:66.
  84. Dandonna S et al. Gene Dosage of the Common Variant 9p21 Predicts Severity of Coronary Artery Disease. J Am Coll Cardiol. 2010; 56(6):479-488.
  85. Zakrzewski-jakubiak M, De denus S, Dubé MP, Bélanger F, White M, Turgeon J. Ten renin-angiotensin system-related gene polymorphisms in maximally treated Canadian Caucasian patients with heart failure. Br J Clin Pharmacol. 2008;65(5):742-51.
  86. Wang WZ. Association between T174M polymorphism in the angiotensinogen gene and risk of coronary artery disease: a meta-analysis. J Geriatr Cardiol. 2013; 10:59-65.
  87. Touyz RM and EL Schiffrin. Signal Transduction Mechanisms Mediating the Physiological and Pathophysiological Actions of Angiotensin II in Vascular Smooth Muscle Cells. Pharmacol Rev. 2000; 52(4):639-672.
  88. Catt KJ et al. Angiotensin II blood-levels in human hypertension. The Lancet. 1971; 297:459-464.
  89. Million Hearts: strategies to reduce the prevalence of leading cardiovascular disease risk factors. United States, 2011. MMWR 2011; 60(36):1248–51.
  90. Li X et al. AGT gene polymorphisms (M235T, T174M) are associated with coronary heart disease in a Chinese population. J Renin Angiotensin Aldosterone Syst. 2013; 14(4):354-9.
  91. Gardemann A et al. Angiotensinogen T174M and M235T gene polymorphisms are associated with the extent of coronary atherosclerosis. Atherosclerosis. 1999; 145(2):309-14.
  92. Irvin MR, Kabagambe EK, Tiwari HK, et al. Apolipoprotein E polymorphisms and postprandial triglyceridemia before and after fenofibrate treatment in the Genetics of Lipid Lowering and Diet Network (GOLDN) Study. Circ Cardiovasc Genet. 2010;3(5):462-7.
  93. Zende PD, Bankar MP, Kamble PS, Momin AA. Apolipoprotein e gene polymorphism and its effect on plasma lipids in arteriosclerosis. J Clin Diagn Res. 2013;7(10):2149-52.
  94. Mahley RW et al. Apolipoprotein E: Far More Than a Lipid Transport Protein. Annu Rev Genomics Hum Genet. 2000; 1:507-537.
  95. Eichner JE et al. Apolipoprotein E Polymorphism and Cardiovascular Disease: A HuGE Review. Am J Epidemiol. 2002; 155(6):487-495.
  96. Villeneuve S et al. The potential applications of Apolipoprotein E in personalized medicine. Front Aging Neurosci. 2014; 6:154.
  97. Howard BV et al. Association of Apolipoprotein E Phenotype with Plasma Lipoproteins in African-American and White Young Adults. Am J Epidemiol. 1998; 148(9):859-868.
  98. Yassine H. et al. DHA brain uptake and APOE4 status: a PET study with (1-11C)-DHA. Alzheimer’s Research & Therapy 2017; 9:23.
  99. Casas JP et al. Endothelial Nitric Oxide Synthase Genotype and Ischemic Heart Disease: Meta-Analysis of 26 Studies Involving 23,028 Subjects. Circulation. 2004; 109:1359-1365.
  100. Luo JQ, Wen JG, Zhou HH, Chen XP, Zhang W. Endothelial nitric oxide synthase gene G894T polymorphism and myocardial infarction: a meta-analysis of 34 studies involving 21,068 subjects. PLoS ONE. 2014;9(1):e87196.
  101. Alkaitis M et al. Recoupling the Cardiac Nitric Oxide Synthases: Tetrahydrobiopterin Synthesis and Recycling. Curr Heart Fail Rep. 2012; 9:200–210.
  102. Xie X et al. Endothelial nitric oxide synthase gene single nucleotide polymorphisms and the risk of hypertension: A meta-analysis involving 63,258 subjects. Clinical and Experimental Hypertension. 2017; 39(2):175-182.
  103. Shengyuan Liu et al. The nitric oxide synthase 3 G894T polymorphism associated with Alzheimer’s disease risk: a meta-analysis. Sci Rep. 2015; 5:13598.
  104. Marsden PA et al. Structure and chromosomal localization of the human constitutive endothelial nitric oxide synthase gene. J Biol Chem. 1992; 68:17478-17488.
  105. Cosentino F and Luscher TF. Maintenance of vascular integrity: role of nitric oxide and other bradykinin mediators. Eur Heart J. 1995; 16 Suppl K:4-12.
  106. Huang PL. eNOS, metabolic syndrome and cardiovascular disease. Trends Endocrinol Metab. 2009; 20(6):295-302.
  107. Hogg N et al. Inhibition of low-density lipoprotein oxidation by nitric oxide. Potential role in atherogenesis. FEBS Lett. 1993; 334(2):170-174.
  108. Radomski MW et al. Endogenous nitric oxide inhibits human platelet adhesion to vascular endothelium. Lancet. 1987; 2:1057-1058.
  109. Tesauro M et al. Intracellular processing of endothelial nitric oxide synthase isoforms associated with differences in severity of cardiopulmonary diseases: cleavage of proteins with aspartate vs. glutamate at position 298. Proc Natl Acad Sci U S A. 2000; 6:2832-2835.
  110. Niu W and Y Qi. An Updated Meta-Analysis of Endothelial Nitric Oxide Synthase Gene: Three Well-Characterized Polymorphisms with Hypertension. Plos One. 2011; 6(9):e24266.
  111. Wang M et al. Association of G894T polymorphism in endothelial nitric oxide synthase gene with the risk of ischemic stroke: A meta-analysis. Biomed Rep. 2013; 1(1):144-150.
  112. Zigra AM et al. eNOS gene variants and the risk of premature myocardial infarction. Dis Markers. 2013; 34(6):431-436.
  113. Gilbody S et al. Methylenetetrahydrofolate Reductase (MTHFR) Genetic Polymorphisms and Psychiatric Disorders: A HuGE Review. Am J Epidemiol. 2007; 165:1-13.
  114. Ho V et al. Effects of methionine synthase and methylenetetrahydrofolate reductase gene polymorphisms on markers of one-carbon metabolism. Genes Nutr. 2013; 8(6):571-80.
  115. Agata R. et al. The MAOA, COMT, MTHFR and ESR1 gene polymorphisms are associated with the risk of depression in menopausal women. Maturitas 84. 2016; 84:42–54.
  116. Van der Put NM et al. A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects? Am J Hum Genet. 1998; 62(5):1044–51.
  117. Wagner C. Biochemical role of folate in cellular metabolism. In: Bailey LB, editor. Folate in health and disease. New York, NY: Marcel Dekker Inc.; 1995. p. 23–42.
  118. Bailey LB and JF Gregory III. Polymorphisms of Methylenetetrahydrofolate Reductase and Other Enzymes: Metabolic Significance, Risks and Impact on Folate Requirement. J Nutr. 1999; 129(5):919-22.
  119. Stover PJ. Polymorphisms in 1-Carbon Metabolism, Epigenetics and Folate-Related Pathologies. J. Nutrigenet Nutrigenomics. 2012; 4(5):293-305.
  120. Refsum H et al. The Hordaland Homocysteine Study: A Community-Based Study of Homocysteine, Its Determinants, and Associations with Disease. J Nutr. 2006; 136:1731S-1740S.
  121. Frosst P et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 1995; 10:111–113.
  122. Weisberg I et al. A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Mol Genet Metab. 1998; 64:169–72.
  123. Teng Z. The 677C>T (rs1801133) polymorphism in the MTHFR gene contributes to colorectal cancer risk: a meta-analysis based on 71 research studies. PLoS One. 2013; 8(2):e55332.
  124. Yang L, et al. Impact of methylenetetrahydrofolate reductase (MTHFR) polymorphisms on methotrexate-induced toxicities in acute lymphoblastic leukemia: a meta-analysis. Tumor Biol. 2012; 33(5):1445–54.
  125. Bjelland I et al. Folate, Vitamin B12, Homocysteine, and the MTHFR 677CT Polymorphism in Anxiety and Depression: The Hordaland Homocysteine Study. Arch Gen Psychiatry. 2003; 60(6):618-626.
  126. Beydoun MA et al. Serum folate, vitamin B-12 and homocysteine and their association with depressive symptoms among US adults. Psychosom Med. 2010; 72(9):862-873.
  127. Nurk E et al. Plasma Total Homocysteine and Memory in the Elderly: The Hordaland Homocysteine Study. Ann Neurol. 2005; 58:847-857.
  128. Rajagopalan P et al. Common folate gene variant, MTHFR C677T, is associated with brain structure in two independent cohorts of people with mild cognitive impairment. Neuroimage Clin. 2012; 1(1):179-187.
  129. Lewis SJ et al. The thermolabile variant of MTHFR is associated with depression in the British Women’s Heart and Health Study and a meta-analysis. Molecular Psychiatry. 2006; 11:352-360.
  130. Steluti J et al. Genetic Variants Involved in One-Carbon Metabolism: Polymorphism Frequencies and Differences in Homocysteine Concentrations in the Folic Acid Fortification Era. Nutrients 2017; 9:539.
  131. Chen D, et al. Folate metabolism genetic polymorphisms and meningioma and glioma susceptibility in adults. Oncotarget 2017; 8(34): 57265-57277.
  132. Lim U et al. Gene-nutrient interactions among determinants of folate and one-carbon metabolism on the risk of non-Hodgkin lymphoma: NCI-SEER Case-Control Study. 2007; 109:3050-3059.
  133. Han X et al. Genetic variants and increased risk of meningioma: an updated meta-analysis. OncoTargets and Therapy. 2017; 10:1875–1888.
  134. Carr DF, O’meara H, Jorgensen AL, et al. SLCO1B1 genetic variant associated with statin-induced myopathy: a proof-of-concept study using the clinical practice research datalink. Clin Pharmacol Ther. 2013;94(6):695-701.
  135. Donnelly LA, Doney AS, Tavendale R, et al. Common nonsynonymous substitutions in SLCO1B1 predispose to statin intolerance in routinely treated individuals with type 2 diabetes: a go-DARTS study. Clin Pharmacol Ther. 2011;89(2):210-6.
  136. Niemi M et al. Organic Anionic Transporting Protein 1B1: a Genetically Polymorphic Transporter of Major Importance for Hepatic Drug Uptake. Pharm Review. 2011; 63(1):157-181.
  137. Ramsey LB et al. The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1 and Simvastatin-Induced Myopathy: 2014 Update. Clin Pharmacol Ther. 2014; 96(4):423-428.
  138. Huang Y et al. Association between prediabetes and risk of cardiovascular disease and all-cause mortality: systematic review and meta-analysis. 2016; 355:i5953.
  139. Ma C. et al. Effects of weight loss interventions for adults who are obese on mortality, cardiovascular disease, and cancer: systematic review and meta-analysis. BMJ 2017; 359:j4849.
  140. Meikle J et al. Exercise in a Healthy Heart Program: A Cohort Study. Cardiology 2013; 7:145–151.
  141. Alessandro A et al. Mediterranean Diet and Cardiovascular Disease: A critical Evaluation of A Priori Dietary Indexes.  2015; 7:7863-7888.
  142. Akarolo-Anthony S et al. Plasma Magnesium and the Risk of Ischemic Stroke among Women. Stroke 2014; 45(10): 2881–2886.
  143. Lee S et el. The relationship between Magnesium and Endothelial Function in End-Stage Renal Disease Patients on Hemodialysis. Yonsei Med J 2016; 57(6):1446-1453.
  144. Ashor A et al. Effect of vitamin C and vitamin E supplementation on endothelial function: a systematic review and meta-analysis of randomized controlled trials. British Journal of Nutrition 2015; 113:1182–1194.
  145. Wilson A et al. Functionally Null Mutations in Patients with the cblG-Variant Form of Methionine Synthase Deficiency. Am. J. Hum. Genet. 1998; 63:409–414.
  146. Saita E et al. Anti-inflammatory Diet for Atherosclerosis and Coronary Artery Disease: Antioxidant Foods. Clinical Medicine Insights:  Cardiology 2014; 8(S3) 61-65.
  147. Hosogoe N et al. Add-on Antiplatelet Effects of Eicosapentaenoic Acid with Tailored Dose Setting in Patients on Dual Antiplatelet Therapy. Int Heart J. 2017; 58(4): 481-485.
  148. Ho, H. T. et al. A systematic review and meta-analysis of randomized controlled trials of the effect of konjac glucomannan, a viscous soluble fiber, on LDL cholesterol and the new lipid targets non-HDL cholesterol and apolipoprotein B. Am J Clin Nutr. 2017; 105(5):1239-1247.
  149. Zelman, K. Fiber: How Much Do I Need? WebMD. 2011 https://www.webmd.com/diet/guide/fiber-how-much-do-you-need#1.
  150. Nordmann A et al. Effects of Low-Carbohydrate vs Low-fat Diets on Weight loss and Cardiovascular Risk Factors. Arch Intern Med. 2006; 166:285-293.
  151. Huang Y et al. Association between prediabetes and risk of cardiovascular disease and all-cause mortality: systematic review and meta-analysis. 2016; 355:i5953.
  152. Ferrucci L et al. Common Variation in the B-Carotene 15, 15’-Monooxygenase 1 Gene Affects Circulating Levels of Carotenoids: A Genome-wide Association Study. The American Journal of Human Genetics. 2009; 84, 123-133.
  153. Lietz G et al. Single Nucleotide Polymorphisms Upstream from the B-Carotene 15, 15’-Monoxygenase Gene Influence Provitamin A Conversion Efficiency in Female Volunteers. J. Nutr. 2012; 142(1):161S-165S
  154. Borel P et al. Genetic Variations Involved in Interindividual Variability in Carotenoid Status. Mol Nutr Food Res. 2012; 56(2): 228-40.
  155. Wyss A et al. Expression pattern and localization of β,β-carotene 15,15′-dioxygenase in different tissues. Biochem. J. 2001; 354:521–529.
  156. Li LH, Yin XY, Wu XH, et al. Serum 25(OH)D and vitamin D status in relation to VDR, GC and CYP2R1 variants in Chinese. Endocr J. 2014;61(2):133-41.
  157. Nissen J et al. Common Variants in CYP2R1 and GC Genes Predict Vitamin D Concentrations in Healthy Danish Children and Adults. PLoS One. 2014; 9(2):e89907.
  158. Cheng JB et al. Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25-hydroxylase. Proc Natl Acad Sci U S A. 2004; 101:7711–7715.
  159. Ahn J et al. Genome-wide association study of circulating vitamin D levels. Human Molecular Genetics. 2010; 19(13): 2739-2745.
  160. Harris HW et al. Supplementation might help patients with depression, seasonal mood disturbances. Current Psych. 2013; 12(4):19-25.
  161. Houssein-Nezhad A et al. Vitamin D for Health: A Global Perspective. Mayo Clin. Proc. 2013; 88(7):720-755.
  162. Holick MF and M Garabedian. Vitamin D: photobiology, metabolism, mechanism of action, and clinical applications. In: Favus MJ, ed. Primer on the metabolic bone diseases and disorders of mineral metabolism. 6th ed. Washington, DC: American Society for Bone and Mineral Research. 2006; 129-137.
  163. Lips P and NM van Schoor. The effect of vitamin D on bone and osteoporosis. Best Pract Res Clin Endocrinol Metab. 2011; 25:585–591.
  164. Wang T et al. Common genetic determinants of vitamin D insufficiency: a genome-wide association study. Lancet. 2010; 376(9736):180-188.
  165. Bischoff-Ferrari HA et al. A pooled analysis of vitamin D dose requirements for fracture prevention. N Engl J Med. 2012; 367:40–9.
  166. Grober U et al. Vitamin D: Update 2013: From rickets prophylaxis to general preventive healthcare. Dermato-Endocrinology. 2013; 5(3):331-47.
  167. Seppälä et al. Association between vitamin b12 levels and melancholic depressive symptoms: a Finnish population-based study. BMC Psychiatry 2013; 13:145.
  168. Tanaka T et al. Genome-wide Association Study of Vitamin B6, Vitamin B12, Folate, and Homocysteine Blood Concentrations. The American Journal of Human Genetics. 2009; 84:477-482.
  169. Hazra A et al. Common variants of FUT2 are associated with plasma vitamin B12 levels. Nat. Genet. 2008; 40:1160–1162.
  170. Kelly RJ et al. Sequence and expression of a candidate for the human Secretor blood group alpha (1,2)fucosyltransferase gene (FUT2). Homozygosity for an enzyme-inactivating nonsense mutation commonly correlates with the non-secretor phenotype. J Biol Chem. 1995; 270:4640–4649.
  171. Hazra A et al. Genome-wide significant predictors of metabolites in the one-carbon metabolism pathway. Hum Mol Gen. 2009; 18(23):4677-4687.
  172. Semmes BJ. Depression: a role for omega-3 fish oils and B vitamins? Evid. Based Integr. Med. 2005; 2:229–237.
  173. Tiemeier H et al. Vitamin B12, Folate, and Homocysteine in Depression: The Rotterdam Study. Am J Psychiatry. 2002; 159:2099-2101.
  174. Frankenburg, FR. The role of one-carbon metabolism in schizophrenia and depression. Harv. Rev. Psychiatry. 2007; 15:146–160.
  175. Wang W, Ingles SA, Torres-mejía G, et al. Genetic variants and non-genetic factors predict circulating vitamin D levels in Hispanic and non-Hispanic White women: the Breast Cancer Health Disparities Study. Int J Mol Epidemiol Genet. 2014;5(1):31-46.
  176. Nissen J et al. Common Variants in CYP2R1 and GC Genes Predict Vitamin D Concentrations in Healthy Danish Children and Adults. PLoS One. 2014; 9(2):e89907.
  177. Gozdzik A et al. Association of vitamin D binding protein (VDBP) polymorphisms and serum 25(OH)D concentrations in a sample of young Canadian adults of different ancestry. J Steroid Biochem Mol Biol. 2011; 127:405–412.
  178. Ahn J et al. Genome-wide association study of circulating vitamin D levels. Human Molecular Genetics. 2010; 19(13) 2739-2745.
  179. Foucan L et al. Polymorphisms in GC and NADSYN1 Genes are associated with vitamin D status and metabolic profile in non-diabetic adults. BMC Endocrine Disorders. 2013; 13:36.
  180. Wang T et al. Common genetic determinants of vitamin D insufficiency: a genome-wide association study. Lancet. 2010; 376(9736):180-188.
  181. Grober U et al. Vitamin D: Update 2013: From rickets prophylaxis to general preventive healthcare. Dermato-Endocrinology. 2013; 5(3):331-47.
  182. Bischoff-Ferrari HA et al. A pooled analysis of vitamin D dose requirements for fracture prevention. N Engl J Med. 2012; 367:40–9.
  183. Foucan L, Vélayoudom-céphise FL, Larifla L, et al. Polymorphisms in GC and NADSYN1 Genes are associated with vitamin D status and metabolic profile in Non-diabetic adults. BMC Endocr Disord. 2013;13:36.
  184. Wang T et al. Common genetic determinants of vitamin D insufficiency: a genome-wide association study. Lancet. 2010; 376(9736):180-188.
  185. Hara N et al. Molecular identification of human glutamine- and ammonia-dependent NAD synthetases. Carbon-nitrogen hydrolase domain confers glutamine dependency. J. Biol. Chem. 2003; 278(13):10914-10921.
  186. Wassif CA et al. Mutations in the human sterol Δ7-reductase gene at 11q12–13 cause Smith–Lemli–Opitz syndrome. Am. J. Hum. Genet. 1998; 63:55–62.
  187. Harris HW et al. Supplementation might help patients with depression, seasonal mood disturbances. Current Psych. 2013; 12(4):19-25.
  188. Houssein-Nezhad A et al. Vitamin D for Health: A Global Perspective. Mayo Clinic. Proc. 2013; 88(7):720-755.
  189. Bischoff-Ferrari HA et al. A pooled analysis of vitamin D dose requirements for fracture prevention. N Engl J Med. 2012; 367:40–9.
  190. Grober U et al. Vitamin D: Update 2013: From rickets prophylaxis to general preventive healthcare. Dermato-Endocrinology. 2013; 5(3):331-47.
  191. Benyamin B et al. Common variants in TMPRSS6 are associated with iron status and erythrocyte volume. Nature Genetics 2009; 41:1173-1175.
  192. Chambers JC et al. Genome-wide association study identifies variants in TMPRSS6 associated with hemoglobin levels. Nature Genetics 2009; 41:1170-1172.
  193. Stoltzfus RJ. Iron deficiency: global prevalence and consequences. Food Nutrition Bulletin. 2003; 24:S99–S103.
  194. Patel KV. Variability and heritability of hemoglobin concentration: an opportunity to improve understanding of anemia in older adults. Haematologica 2008; 93:1281-1283.
  195. Mccullough ML, Stevens VL, Diver WR, et al. Vitamin D pathway gene polymorphisms, diet, and risk of postmenopausal breast cancer: a nested case-control study. Breast Cancer Res. 2007;9(1):R9. Morris HA. Vitamin D Activities for Health Outcomes. Ann Lab Med 2014; 34:181-186.
  196. Palomba S et al. BsmI vitamin D receptor genotypes influence the efficacy of antiresorptive treatments in postmenopausal osteoporotic women. A 1-year multicenter, randomized and controlled trial. Osteoporosis Int. 2005; 16(8):943-52.
  197. Jia F, Sun RF, Li QH, et al. Vitamin D receptor BsmI polymorphism and osteoporosis risk: a meta-analysis from 26 studies. Genet Test Mol Biomarkers. 2013;17(1):30-4.
  198. Turner AG. Vitamin D and bone health. Scand J Clin Lab Invest Suppl. 2012; 243:65-72.
  199. Jia F et al. Vitamin D receptor BsmI polymorphism and osteoporosis risk: a meta-analysis from 26 studies. Genet Test Mol Biomarkers. 2013; 17(1):30-4.
  200. Ji GR. BsmI, TaqI, ApaI and FokI polymorphisms in the vitamin D receptor (VDR) gene and risk of fracture in Caucasians: a meta-analysis. Bone. 2010; 47(3):681-6.
  201. Vaughan-Shaw PG et al. The impact of vitamin D pathway genetic variation and circulating 25-hydroxyvitamin D on cancer outcome: Systemic review and meta-analysis. Br. J. Cancer 2017; 116:1092-1110.
  202. Deuster E et al. Vitamin D and VDR in Gynecological Cancers – A Systematic Review. Intl J Mol Sci 2017; 18:2328-2340.
  203. Gnagnarella P et al. Vitamin D receptor polymorphism FokI and cancer risk. A comprehensive meta-analysis. Carcinogenesis. 2014; 35:1913-1919.
  204. Laczmanski L et al. Association of the vitamin D receptor FokI gene polymorphism with sex- and non-sex-associated cancers: A meta-analysis. Tumor Biol 2017; 39(10):1-8.
  205. Mun M, Kim TH, Hwang JY, Jang WC. Vitamin D receptor gene polymorphisms and the risk for female reproductive cancers. Maturitas. 2015; 81(2):256-65.
  206. Muscogiuri G et al. Mechanisms in Endocrinology: Vitamin D as a potential contributor in endocrine health and disease. Eur J Endocrinol 2014; 171(3):R101-R110.
  207. Bagheri M et al. Vitamin D Receptor TaqI Gene Variant in Exon 9 and Polycystic Ovary Syndrome Risk. Int J Fertil Steril. 2013; 7(2):116-121.
  208. Reis G et al. Vitamin D receptor polymorphisms and the polycystic ovary syndrome: A systematic review. J. Obstet. Gynaecol Res 2017; 43(3):436-446.
  209. El-Shal AS et al. Genetic variation in the vitamin D receptor gene and vitamin D serum levels in Egyptian women with polycystic ovary syndrome. Mol Biol Rep 2013; 40(11):6063.
  210. Pal L et al. Vitamin D Status Relates to Reproductive Outcome in Women with Polycystic Ovary Syndrome: Secondary Analysis of a Multicenter Randomized Controlled Trial. J Clin Endocrinol Metab. 2016; 101(8):3027–3035.
  211. Mahley RW et al. Apolipoprotein E: Far More Than a Lipid Transport Protein. Annu Rev Genomics Hum Genet. 2000; 1:507-537.
  212. Eichner JE et al. Apolipoprotein E Polymorphism and Cardiovascular Disease: A HuGE Review. Am J Epidemiol. 2002; 155(6):487-495.
  213. Villeneuve S et al. The potential applications of Apolipoprotein E in personalized medicine. Front Aging Neurosci. 2014; 6:154.
  214. Howard BV et al. Association of Apolipoprotein E Phenotype with Plasma Lipoproteins in African-American and White Young Adults. Am J Epidemiol. 1998; 148(9):859-868.
  215. Yassine H. et al. DHA brain uptake and APOE4 status: a PET study with (1-11C)-DHA. Alzheimer’s Research & Therapy 2017; 9:23.
  216. Yassine H et al. Association of Docosahexaenoic Acid Supplementation With Alzheimer Disease Stage in Apolipoprotein E e4 Carriers: A Review. JAMA Neurol. 2017 March 01; 74(3): 339–347.
  217. Enoch MA, Xu K, Ferro E, Harris CR, Goldman D. Psychiatr Genet. 2003;13(1):33-41.
  218. Smolka MN, Schumann G, Wrase J, et al. Catechol-O-methyltransferase val158met genotype affects processing of emotional stimuli in the amygdala and prefrontal cortex. J Neurosci. 2005;25(4):836-42.
  219. Lacerda-pinheiro SF, Pinheiro junior RF, Pereira de lima MA, et al. Are there depression and anxiety genetic markers and mutations? A systematic review. J Affect Disord. 2014;168:387-98.
  220. Mier D et al. Neural substrates of pleiotropic action of genetic variation in COMT: a meta-analysis. Molecular Psychiatry 2010; 15:918-927.
  221. Agata R. et al. The MAOA, COMT, MTHFR and ESR1 gene polymorphisms are associated with the risk of depression in menopausal women. Maturitas 2016; 84:42–54.
  222. Crooke P et al. Estrogens, Enzyme Variants, and Breast Cancer: A Risk Model. Cancer Epidemiol Biomarkers Prev 2006; 15(9):1620-9.
  223. Lachman H et al. Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders. Pharmacogenetics 1996; 6:243-250.
  224. Weinshilboum R et al. Methylation Pharmacogenetics: Catechol-O methyltransferase, Thiopurine Methyltransferase, and Histamine N-Methyltransferase. Annu. Rev. Pharmacol. Toxicol. 1999; 39:19-52.
  225. Mannisto P and S Kaakkola. Catechol-O-methyltransferase (COMT): Biochemistry, Molecular Biology, Pharmacology, and Clinical Efficacy of the New Selective COMT Inhibitors. Pharm Rev. 1999; 51(4):594-622.
  226. Dawling S et al. Catechol-O-Methyltransferase (COMT)-mediated Metabolism of Catechol Estrogens: Comparison of Wild-Type and Variant COMT Isoforms. Cancer Res. 2001; 61:6716-6722.
  227. Goldman D et al. The Genetics of Addictions: Uncovering the Genes. Nat Rev Genet. 2005; 6(7):521-532.
  228. Yuferov V et al. Search for Genetic Markers and Functional Variants Involved in the Development of Opiate and Cocaine Addiction, and Treatment. Ann N Y Acad Sci. 2010; 1187:184-207.
  229. Schellekens AF et al. COMT Val158Met modulates the effect of childhood adverse experiences on the risk of alcohol dependence. Addict Biol. 2013; 18(2):344-356.
  230. Bhakta SG et al. The COMT Met158 allele and violence in schizophrenia: a meta-analysis. Schizophr Res. 2012; 140(1-3):192-197.
  231. Godar SC and M Bortolato. Gene-sex interactions in schizophrenia: focus on dopamine neurotransmission. Front Behav Neurosci. 2014; 8:71.
  232. Pooley EC et al. The met158 allele of catechol-o-methyltransferase (COMT) is associated with obsessive-compulsive disorder in men: case-control study and meta-analysis. Mol Psych. 2007; 12:556-551.
  233. Konishi Y et al. Genexgenexgender interaction of BDNF and COMT genotypes associated with panic disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2014; 51:119-125.
  234. Kolassa IT et al. The risk of posttraumatic stress disorder after trauma depends on traumatic load and the catechol-o-methyltransferase Val(158)Met polymorphism. Biol Psychiatry. 2010; 67(4):304-308.
  235. Lee SY et al. COMT and BDNF interacted in bipolar II disorder not comorbid with anxiety disorder. Behav Brain Res. 2013; 237:243-248.
  236. Zhang Z. The Val/Met functional polymorphism in COMT confers susceptibility to bipolar disorder: evidence from an association study and a meta-analysis. J Neural Transm. 2009; 116(10):1193-200.
  237. Janicki PK. Pharmacogenetics of Pain Management. Comprehensive Treatment of Chronic Pain by Medical, Interventional, and Integrative Approaches. Edited by TR Deers. American Academy of Pain Medicine. 2013.
  238. Zubieta JK et al. COMT val158met Genotype Affects mu-opioid Neurotransmitter Responses to a Pain Stressor. Science. 2003; 299(5610):1240-1243.
  239. Klepstad P et al. Genetic variability and clinical efficacy of morphine. Acta Anasthesiol Scand. 2005; 49:902-908.
  240. Mannisto PT and S Kaakkola. Catechol-O-methyltransferase (COMT): Biochemistry, Molecular Biology, Pharmacology, and Clinical Efficacy of the New Selective COMT Inhibitors. Pharm Rev. 1999; 51(4):594-622.
  241. Corvol JC et al. The COMT Val158Met polymorphism affects the response to entacapone in Parkinson’s disease: a randomized crossover clinical trial. Ann Neurol. 2011; 69(1):111-118.
  242. Ball P and R Knuppen. Catecholoestrogens (2-and 4-hydroxyoestrogens): chemistry, biogenesis, metabolism, occurrence and physiological significance. Acta Endocrinol. Suppl. 1980; 232:1-127.
  243. Lakhani NJ et al. 2-Methoxyestradiol, a Promising Anticancer Agent. Pharmacotherapy. 2003; 23:165-172.
  244. Lavigne JA et al. The Effects of Catechol-O-Methyltransferase Inhibition on Estrogen Metabolite and Oxidative DNBA Damage Levels in Estradiol-treated MCF-7 Cells. Cancer Research. 2001; 61:7488-7494.
  245. Worda C et al. Influence of the catechol-O-methyltransferase (COMT) codon 158 polymorphism on estrogen levels in women. Human Reproduction. 2003; 18(2):262-266.
  246. Eriksson AL et al. The COMT val158met polymorphism Is Associated with Early Pubertal Development, Height and Cortical Bone Mass in Girls. Pediatr Res. 2005; 58(1):71-77.
  247. Masurier M et al. Effect of Acute Tyrosine Depletion in Using a Branched Chain Amino-Acid Mixture on Dopamine Neurotransmission in the Rat Brain. Neuropsychopharmacology. 2006; 31(2):310-317.
  248. Sarris J et al. S-adenosyl methionine (SAMe) versus escitalopram and placebo in major depression RCT: Efficacy and effects of histamine and carnitine as moderators of response. J Affect Disord. 2014; 164:76-81.
  249. Kennedy D et al. Effects of high-dose B vitamin complex with vitamin C and minerals on subjective mood and performance in healthy males. Psychopharmacology (Berl). 2010; 211(1):55-68.
  250. Li Y et al. Functional and structural comparisons of cysteine residues in the Val108 wild type and Met108 variant of human soluble catechol O-methyltransferase. Chem Biol Interact. 2005; 152(2-3):151-163.
  251. Fava M et al. Rapidity of onset of the antidepressant effect of parenteral S-adenosyl-l-methionine. Psychiatry Res. 1995; 56(3):295-297.
  252. Jeffery DR and JA Roth. Kinetic reaction mechanism for magnesium binding to membrane-bound and soluble catechol O-methyltransferase. Biochem. 1987; 26(10):2955-2958.
  253. Sowa-Kucma M et al. Zinc, magnesium and NMDA receptor alterations in the hippocampus of suicide victims. J Affect Disord. 2013; 151(3):924-931.
  254. Basheer MP et al. A study of serum magnesium, calcium and phosphorus level, and cognition in the elderly population of South India. Alexandria J Med. 2016; 52(4):303-308.
  255. Yary T et al. Dietary magnesium intake and the incidence of depression: A 20 year follow-up study. J Affect Disord. 2016; 193:94-98.
  256. Haan MN et al. Homocysteine, B vitamins, and the incidence of dementia and cognitive impairment: Results from the Sacramento Area Latino Study on Aging. Am J Clin Nutr. 2007; 85(2):511-517.
  257. Smith AD et al. Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: A randomized controlled trial. PLoS One. 2010; 5(9):1-10.
  258. Mitchell ES et al. B vitamin polymorphisms and behavior: Evidence of associations with neurodevelopment, depression, schizophrenia, bipolar disorder and cognitive decline. Neurosci Biobehav Rev. 2014; 47:307-320.
  259. Hiroi T et al. Dopamine formation from tyramine by CYP2D6. Biochem Biophys Res Commun. 1998; 249(3):838-843.
  260. Zhu ZT et al. Tyramine excites rat subthalamic neurons in vitro by a dopamine-dependent mechanism. Neuropharmacology. 2007; 52(4):1169-1178.
  261. Burchett SA et al. The mysterious trace amines: Protean neuromodulators of synaptic transmission in mammalian brain. Prog Neurobiol. 2006; 79:223-246.
  262. Papaleo F et al. Sex-dichotomous effects of functional COMT genetic variations on cognitive functions disappear after menopause in both health and schizophrenia. Eur Neuropsychopharmacol. 2015; 25(12):2349-2363.
  263. Almey A et al. Estrogen receptors in the central nervous system and their implication for dopamine-dependent cognition in females. Horm Behav. 2015; 74:125-138.
  264. McCann S et al. Changes in 2-hydroxyestrone and 16α-hydroxyestrone metabolism with flaxseed consumption: Modification by COMT and CYP1B1 genotype. Cancer Epidemiol Biomarkers Prev. 2007; 16(2):256-262.
  265. Rižner TL. Estrogen biosynthesis, phase I and phase II metabolism, and action in endometrial cancer. Mol Cell Endocrinol. 2013; 381(1-2):124-139.
  266. Masurier M et al. Effect of Acute Tyrosine Depletion in Using a Branched Chain Amino-Acid Mixture on Dopamine Neurotransmission in the Rat Brain. 2006; 31(2):310-317.
  267. Fernstrom HD and MH Fernstrom. Tyrosine, Phenylalanine, and Catecholamine Synthesis and Function in the Brain. J. Nutr. 2007; 137(6):1539S-1547S.
  268. Reus G et al. Kynurenine pathway dysfunction in the pathophysiology and treatment of depression: Evidences from animal and human studies. J Psychiatr Res. 2015; 68:316-328.
  269. Jangid P et al. Comparative study of efficacy of l-5-hydroxytryptophan and fluoxetine in patients presenting with first depressive episode. Asian J Psychiatr. 2013; 6(1):29-34.
  270. Lowe S et al. L-5-Hydroxytryptophan augments the neuroendocrine response to a SSRI. Psychoneuroendocrinology. 2006; 31(4):473-484.
  271. Lardner A et al. Neurobiological effects of the green tea constituent theanine and its potential role in the treatment of psychiatric and neurodegenerative disorders. Nutritional Neuroscience. 2014; 17(4):145-155.
  272. Mu W et al. An overview of biological production of L-theanine. Biotechnol Adv. 2015; 33(3-4):335-342.
  273. Kakuda T. Neuroprotective effects of theanine and its preventive effects on cognitive dysfunction. Pharmacol Res. 2011; 64(2):162-168.
  274. Tian X et al. Protective effect of l-theanine on chronic restraint stress-induced cognitive impairments in mice. Brain Res. 2013; 1503:24-32.
  275. Martínez-Banaclocha M et al. N-acetyl-cysteine in the treatment of Parkinson’s disease. What are we waiting for? Med Hypotheses. 2012; 79(1):8-12.
  276. Dean O et al. N-acetyl cysteine restores brain glutathione loss in combined 2-cyclohexene-1-one and d-amphetamine-treated rats: Relevance to schizophrenia and bipolar disorder. Neurosci Lett. 2011; 499(3):149-153.
  277. Botsakis K et al. 17β-Estradiol/N-acetylcysteine interaction enhances the neuroprotective effect on dopaminergic neurons in the weaver model of dopamine deficiency. Neuroscience. 2016; 320:221-229.
  278. Tunbridge E et al. Polymorphisms in the catechol‐O‐methyltransferase (COMT) gene influence plasma total homocysteine levels. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 147.6 (2008):996-999.
  279. Paul R et al. The potential physiological crosstalk and interrelationship between two sovereign endogenous amines, melatonin and homocysteine. Life Sci. 2015; 139:97-107.
  280. Hursel R et al. The Role of Catechol-o-Methyl Transferase Val (108/158) MET Polymorphism (rs4680) in the effect of Green Tea on Resting Energy Expenditure and Fat Oxidation: A Pilot Study. 2014; 9(9): e106220.
  281. Lorenz M et al. The activity of catechol-O-methyltransferase (COMT) is not impaired by high doses of epigallocatechin-3-gallate (EGCG) in vivo. Eur J Pharmacol. 2014; 740: 645-651.
  282. Kang K et al. Beneficial effects of natural phenolics on levodopa methylation and oxidative neurodegeneration. Brain Res. 2013; 1497:1-14.
  283. Kang K et al. Dual beneficial effects of (-)-epigallocatechin-3-gallate on levodopa methylation and hippocampal neurodegeneration: In vitro and in vivo studies. PLoS One. 2010; 5(8): e11951.
  284. Xie X et al. Adenosine and dopamine receptor interactions in striatum and caffeine-induced behavioral activation. Comp Med. 2007; 57(6):538-545.
  285. Witte A et al. COMT Val158Met polymorphism modulates cognitive effects of dietary intervention. Front Aging Neurosci. 2010; 2:146.
  286. Voelcker-Rehage C et al. COMT gene polymorphisms, cognitive performance, and physical fitness in older adults. Psychol Sport Exerc. 2015; 20:20-28.
  287. Zhu BT et al. Effects of tea polyphenols and flavonoids on liver microsomal glucuronidation of estradiol and estrone. J Steroid Biochem Mol Biol. 1998; 64(3-4):207-215.
  288. Moon YJ et al. Dietary flavonoids: Effects on xenobiotic and carcinogen metabolism. Toxicol Vitr. 2006; 20 (2): 187-210.
  289. Ullah N et al. Green tea phytocompounds as anticancer: A review. Asian Pacific J Trop Dis. 2016; 6(4):330-336.
  290. Wang L et al. CYP1A1 lle462Val Polymorphism Is Associated with Cervical Cancer Risk in Caucasians Not Asians: A Meta-Analysis. Front. Physiol. 2017; 8:1081.
  291. Wu B et al. Mspl and lle462Val Polymorphisms in CYP1A1 and Overall Cancer Risk: A Meta-Analysis. PLOS ONE 2013; 8(12): e85166.
  292. Crooke P et al. Estrogens, Enzyme Variants, and Breast Cancer: A Risk Model. Cancer Epidemiol Biomarkers Prev. 2006; 15(9).
  293. Wang Y et al. The association of the CYP1A1 lle462Val polymorphism with head and neck cancer risk: evidence based on a cumulative meta-analysis.  OncoTargets and Therapy 2016; 9 2927–2934.
  294. Zeng W et al. CYP1A1 rs1048943 and rs4646903 polymorphisms associated with laryngeal cancer susceptibility among Asian populations: a meta-analysis. J. Cell. Mol. Med. 2016; 20 (2): 287-293.
  295. Zhu X et al. Associations between CYP1A1 rs1048943 A>G and rs4646903. T>C genetic variations and colorectal cancer risk: Proof from 26 case-control studies. Oncotarget 2016; 7 (32):51365-51374.
  296. Lu J et al. Genetic polymorphisms of CYP1A1 and risk of leukemia: a met-analysis. OncoTargets and Therapy 2015; 8: 2883–2902.
  297. Ji YN et al. CYP1A1 Ile462Val Polymorphism Contributes to Lung Cancer Susceptibility among Lung Squamous Carcinoma and Smokers: A Meta-Analysis. PLoS ONE 2012; 7(8): e43397.
  298. Wright C et al. Genetic association study of CYP1A1 polymorphisms identifies risk haplotypes in non-small cell lung cancer. Eur Respir J 2010; 35: 152–159.
  299. Koller DL et al. Meta-analysis of genome-wide studies identifies WNT16 and ESR1 snps associated with bone mineral density in premenopausal women. J Bone Miner Res. 2013; 28(3):547–558.
  300. Styrkarsdottir U et al. Multiple Genetic Loci for Bone Mineral Density and Fractures. N Engl J Med 2008; 358:2355-65.
  301. Loannidis JP et al. Differential genetic effects of ESR1 gene polymorphisms on osteoporosis outcomes. JAMA. 2004; 292(17):2105–2114.
  302. Agata R et al. The MAOA, COMT, MTHFR and ESR1 gene polymorphisms are associated with the risk of depression in menopausal women. Maturitas 2016; 84:42–54.
  303. Li WF et al. Genetics of Osteoporosis: Perspectives for Personalized Medicine. Personalized Medicine 2010; 7(6):655-668.
  304. Raisz LG. Pathogenesis of osteoporosis: concepts, conflicts, and prospects J. Clin. Invest. 2005; 115:3318–3325.
  305. Falahati-Nini A et al. Relative contributions of testosterone and estrogen in regulating bone resorption and formation in normal elderly men. J. Clin. Invest. 2000; 106:1553–1560.
  306. Luo L et al. Association of ESR1 and C6orf97 gene polymorphism with osteoporosis in postmenopausal women. Mol Biol Rep. 2014; 41(5):3235-43.
  307. Wang K et al. Association of estrogen receptor alpha gene polymorphisms with bone mineral density: a meta-analysis. Chinese Med. Journal 2012; 125(14):2589-2597.
  308. Wedren S et al. Estrogen receptor alpha gene polymorphism and endometrial cancer risk- a case-control study. BMC Cancer 2008; 8:322.
  309. Martinaityte I et al. Bone mineral density is associated with vitamin D related rs6013897 and estrogen receptor polymorphism rs4870044: The Tromsø study. PLoS ONE 2017; 12(3):e0173045.
  310. Sheng et al. Prognostic role of methylated GSTP1, p16, ESR1 and PITX2 in patients with breast cancer. Medicine 2017; 96:28.
  311. Lee Y et al. Estrogen receptor 1 PvuII and XbaI polymorphisms and susceptibility to Alzheimer’s disease: a meta-analysis. Genet. Mol. Res. 2015; 14 (3):9361-9369.
  312. Zhou X et al. Eight Functional Polymorphisms in the Estrogen Receptor 1 Gene and Endometrial Cancer Risk: A Meta-Analysis. PLoS ONE 2013; 8(4):e60851.
  313. Zhang J, A cis-phase interaction study of genetic variants within the MAOA gene in major depressive disorder. Biol Psychiatry 2010; 68(9):795-800.
  314. Pinsonneault JK, Papp AC, Sadee W. Allelic mRNA expression of X-linked monoamine oxidase a (MAOA) in human brain: dissection of epigenetic and genetic factors. Human Molecular Genetics. 2006; 15(17):2636-2649.
  315. Leuchter AF, McCracken JT, et al. Monoamine oxidase a and catechol-o-methyltransferase functional polymorphisms and the placebo response in major depressive disorder. J Clin Psychopharmacol. 2009; 29(4):372-7.
  316. Estrada K et al. Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. Nat Genet. 2012; 44(5):491–501.
  317. Koller et al. Meta-analysis of genome-wide studies identifies WNT16 and ESR1 snps associated with bone mineral density in premenopausal women. J Bone Miner Res. 2013; 28(3):547–558.
  318. Kim et al. Wnt signaling in bone formation and its therapeutic potential for bone diseases. Ther Adv Musculoskel Dis. 2013; 5(1):13–31.
  319. Monroe D et al. Update on Wnt signaling in bone cell biology and bone disease. Gene 2012; 492:1–18.
  320. Medina-Gomez et al. Meta-Analysis of Genome-Wide Scans for Total Body BMD in Children and Adults Reveals Allelic Heterogeneity and Age-Specific Effects at the WNT16 Locus. PLOS Genet. 2012; 8(7):e1002718.
  321. Yasko, A. 2005. Genetic ByPass, Using Nutrition to Bypass Genetic Mutations. Matrix Development Publishing.
  322. London, M. CBS Upregulation, Myth or Reality? MIT- Massachusetts Institute of Technology. http://web.mit.edu/london/www/cbs.html.
  323. McEvoy M. March 27 2013. Metabolic Gateways: CBS Mutations & Glutathione. Metabolic Healing Empowering Your Health. https://metabolichealing.com/metabolic-gateways-cbs-gene-mutations-glutathione.
  324. Wang L et al. Modulation of Cystathionine β-Synthase Levels Regulates Total Serum Homocysteine in Mice. American Heart Association Journal. 2004; 94:1318-1324.
  325. Aras O et al. Influence of 699C-T and 1080C-T Polymorphisms of the Cystathionine β-synthase gene on Plasma Homocysteine Levels. Clin Gen. 2000; 58:455-459.
  326. Yasko, A. 2009. Autism: Pathways To Recovery. Neurological Research Institute, LLC.
  327. Stipanuk, M. and I. Ueki. Dealing with methionine/homocysteine sulfur: cysteine metabolism to taurine and inorganic sulfur. J Inherit Metab Dis. 2011; 34(1):17-32.
  328. Rumbeiha, W. et al. Acute hydrogen sulfide-induced neuropathology and neurological sequelae: Challenges for translational neuroprotective research. Ann. N.Y. Acad. Sci. 2016; 1378:5-16.
  329. Ingenbleek, Y. and H. Kimura. Nutritional essentiality of sulfur in health and disease. Nutrition Reviews. 2013; 71(7):413-432.
  330. Alkaitis M et al. Recoupling the Cardiac Nitric Oxide Synthases: Tetrahydrobiopterin Synthesis and Recycling. Curr Heart Fail Rep. 2012; 9:200–210.
  331. Xie X et al. Endothelial nitric oxide synthase gene single nucleotide polymorphisms and the risk of hypertension: A meta-analysis involving 63,258 subjects. Clinical and Experimental Hypertension. 2017; 39(2):175-182.
  332. Shengyuan Liu et al. The nitric oxide synthase 3 G894T polymorphism associated with Alzheimer’s disease risk: a meta-analysis. Sci Rep. 2015; 5:13598.
  333. Marsden PA et al. Structure and chromosomal localization of the human constitutive endothelial nitric oxide synthase gene. J Biol Chem. 1992; 68:17478-17488.
  334. Cosentino F and Luscher TF. Maintenance of vascular integrity: role of nitric oxide and other bradykinin mediators. Eur Heart J. 1995; 16 Suppl K:4-12.
  335. Huang PL. eNOS, metabolic syndrome and cardiovascular disease. Trends Endocrinol Metab. 2009; 20(6):295-302.
  336. Hogg N et al. Inhibition of low-density lipoprotein oxidation by nitric oxide. Potential role in atherogenesis. FEBS Lett. 1993; 334(2):170-174.
  337. Radomski MW et al. Endogenous nitric oxide inhibits human platelet adhesion to vascular endothelium. Lancet. 1987; 2:1057-1058.
  338. Tesauro M et al. Intracellular processing of endothelial nitric oxide synthase isoforms associated with differences in severity of cardiopulmonary diseases: cleavage of proteins with aspartate vs. glutamate at position 298. Proc Natl Acad Sci U S A. 2000; 6:2832-2835.
  339. Casas JP et al. Endothelial Nitric Oxide Synthase Genotype and Ischemic Heart Disease: Meta-Analysis of 26 Studies Involving 23,028 Subjects. Circulation. 2004; 109:1359-1365.
  340. Niu W and Y Qi. An Updated Meta-Analysis of Endothelial Nitric Oxide Synthase Gene: Three Well-Characterized Polymorphisms with Hypertension. Plos One. 2011; 6(9):e24266.
  341. Wang M et al. Association of G894T polymorphism in endothelial nitric oxide synthase gene with the risk of ischemic stroke: A meta-analysis. Biomed Rep. 2013; 1(1):144-150.
  342. Zigra AM et al. eNOS gene variants and the risk of premature myocardial infarction. Dis Markers. 2013; 34(6):431-436.
  343. Agata R. et al. The MAOA, COMT, MTHFR and ESR1 gene polymorphisms are associated with the risk of depression in menopausal women. Maturitas 84. 2016; 84:42–54.
  344. Van der Put NM et al. A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects? Am J Hum Genet. 1998; 62(5):1044–51.
  345. Wagner C. Biochemical role of folate in cellular metabolism. In: Bailey LB, editor. Folate in health and disease. New York, NY: Marcel Dekker Inc.; 1995. p. 23–42.
  346. Bailey LB and JF Gregory III. Polymorphisms of Methylenetetrahydrofolate Reductase and Other Enzymes: Metabolic Significance, Risks and Impact on Folate Requirement. J Nutr. 1999; 129(5):919-22.
  347. Stover PJ. Polymorphisms in 1-Carbon Metabolism, Epigenetics and Folate-Related Pathologies. J. Nutrigenet Nutrigenomics. 2012; 4(5):293-305.
  348. Refsum H et al. The Hordaland Homocysteine Study: A Community-Based Study of Homocysteine, Its Determinants, and Associations with Disease. J Nutr. 2006; 136:1731S-1740S.
  349. Frosst P et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 1995; 10:111–113.
  350. Weisberg I et al. A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Mol Genet Metab. 1998; 64:169–72.
  351. Teng Z. The 677C>T (rs1801133) polymorphism in the MTHFR gene contributes to colorectal cancer risk: a meta-analysis based on 71 research studies. PLoS One. 2013; 8(2):e55332.
  352. Yang L, et al. Impact of methylenetetrahydrofolate reductase (MTHFR) polymorphisms on methotrexate-induced toxicities in acute lymphoblastic leukemia: a meta-analysis. Tumor Biol. 2012; 33(5):1445–54.
  353. Bjelland I et al. Folate, Vitamin B12, Homocysteine, and the MTHFR 677CT Polymorphism in Anxiety and Depression: The Hordaland Homocysteine Study. Arch Gen Psychiatry. 2003; 60(6):618-626.
  354. Beydoun MA et al. Serum folate, vitamin B-12 and homocysteine and their association with depressive symptoms among US adults. Psychosom Med. 2010; 72(9):862-873.
  355. Nurk E et al. Plasma Total Homocysteine and Memory in the Elderly: The Hordaland Homocysteine Study. Ann Neurol. 2005; 58:847-857.
  356. Rajagopalan P et al. Common folate gene variant, MTHFR C677T, is associated with brain structure in two independent cohorts of people with mild cognitive impairment. Neuroimage Clin. 2012; 1(1):179-187.
  357. Gilbody S et al. Methylenetetrahydrofolate Reductase (MTHFR) Genetic Polymorphisms and Psychiatric Disorders: A HuGE Review. Am J Epidemiol. 2007; 165:1-13.
  358. Lewis SJ et al. The thermolabile variant of MTHFR is associated with depression in the British Women’s Heart and Health Study and a meta-analysis. Molecular Psychiatry. 2006; 11:352-360.
  359. Steluti J et al. Genetic Variants Involved in One-Carbon Metabolism: Polymorphism Frequencies and Differences in Homocysteine Concentrations in the Folic Acid Fortification Era. Nutrients 2017; 9:539.
  360. Chen D, et al. Folate metabolism genetic polymorphisms and meningioma and glioma susceptibility in adults. Oncotarget 2017; 8(34): 57265-57277.
  361. Lim U et al. Gene-nutrient interactions among determinants of folate and one-carbon metabolism on the risk of non-Hodgkin lymphoma: NCI-SEER Case-Control Study. 2007; 109:3050-3059.
  362. Han X et al. Genetic variants and increased risk of meningioma: an updated meta-analysis. OncoTargets and Therapy. 2017; 10:1875–1888.
  363. Steluti J et al. Genetic Variants Involved in One-Carbon Metabolism: Polymorphism Frequencies and Differences in Homocysteine Concentrations in the Folic Acid Fortification Era. Nutrients 2017; 9(6):539.
  364. Li WX et al. Homocysteine Metabolism Gene Polymorphisms (MTHFR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G) Jointly Elevate the Risk of Folate Deficiency. Nutrients 2015; 7(8):6670-6687.
  365. Ho V et al. Effects of methionine synthase and methylenetetrahydrofolate reductase gene polymorphisms on markers of one-carbon metabolism. Genes Nutr. 2013; 8(6):571-80.
  366. Wang P et al. Association of MTRR A66G polymorphism with cancer susceptibility: Evidence from 85 studies. J Cancer. 2017; 8(2):266-277.
  367. Han D et al. Methionine synthase reductase A66G polymorphism contributes to tumor susceptibility: evidence from 35 case-control studies. Mol Biol Rep. 2012; 39(2):805-816.
  368. Clark S and J Melki. DNA methylation and gene silencing in cancer: which is the guilty party? Oncogene. 2002; 21(35):5380-5387.
  369. Zeng XT et al. Association of methionine synthase rs1801394 and methionine synthase reductase rs1805087 polymorphisms with meningioma in adults: A meta-analysis. BioMed Rep. 2014; 2(3):432-436.

COMT

  1. Agata R. et al. The MAOA, COMT, MTHFR and ESR1 gene polymorphisms are associated with the risk of depression in menopausal women. Maturitas 2016; 84:42–54.
  2. Crooke P et al. Estrogens, Enzyme Variants, and Breast Cancer: A Risk Model. Cancer Epidemiol Biomarkers Prev 2006; 15(9):1620-9.
  3. Lachman H et al. Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders. Pharmacogenetics 1996; 6:243-250.
  4. Weinshilboum R et al. Methylation Pharmacogenetics: Catechol-O methyltransferase, Thiopurine Methyltransferase, and Histamine N-Methyltransferase. Annu. Rev. Pharmacol. Toxicol. 1999; 39:19-52.
  5. Mannisto P and S Kaakkola. Catechol-O-methyltransferase (COMT): Biochemistry, Molecular Biology, Pharmacology, and Clinical Efficacy of the New Selective COMT Inhibitors. Pharm Rev. 1999; 51(4):594-622.
  6. Dawling S et al. Catechol-O-Methyltransferase (COMT)-mediated Metabolism of Catechol Estrogens: Comparison of Wild-Type and Variant COMT Isoforms. Cancer Res. 2001; 61:6716-6722.
  7. Mier D et al. Neural substrates of pleiotropic action of genetic variation in COMT: a meta-analysis. Molecular Psychiatry 2010; 15:918-927.
  8. Goldman D et al. The Genetics of Addictions: Uncovering the Genes. Nat Rev Genet. 2005; 6(7):521-532.
  9. Yuferov V et al. Search for Genetic Markers and Functional Variants Involved in the Development of Opiate and Cocaine Addiction, and Treatment. Ann N Y Acad Sci. 2010; 1187:184-207.
  10. Schellekens AF et al. COMT Val158Met modulates the effect of childhood adverse experiences on the risk of alcohol dependence. Addict Biol. 2013; 18(2):344-356.
  11. Bhakta SG et al. The COMT Met158 allele and violence in schizophrenia: a meta-analysis. Schizophr Res. 2012; 140(1-3):192-197.
  12. Godar SC and M Bortolato. Gene-sex interactions in schizophrenia: focus on dopamine neurotransmission. Front Behav Neurosci. 2014; 8:71.
  13. Pooley EC et al. The met158 allele of catechol-o-methyltransferase (COMT) is associated with obsessive-compulsive disorder in men: case-control study and meta-analysis. Mol Psych. 2007; 12:556-551.
  14. Konishi Y et al. Genexgenexgender interaction of BDNF and COMT genotypes associated with panic disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2014; 51:119-125.
  15. Kolassa IT et al. The risk of posttraumatic stress disorder after trauma depends on traumatic load and the catechol-o-methyltransferase Val(158)Met polymorphism. Biol Psychiatry. 2010; 67(4):304-308.
  16. Lee SY et al. COMT and BDNF interacted in bipolar II disorder not comorbid with anxiety disorder. Behav Brain Res. 2013; 237:243-248.
  17. Zhang Z. The Val/Met functional polymorphism in COMT confers susceptibility to bipolar disorder: evidence from an association study and a meta-analysis. J Neural Transm. 2009; 116(10):1193-200.
  18. Janicki PK. Pharmacogenetics of Pain Management. Comprehensive Treatment of Chronic Pain by Medical, Interventional, and Integrative Approaches. Edited by TR Deers. American Academy of Pain Medicine. 2013.
  19. Zubieta JK et al. COMT val158met Genotype Affects mu-opioid Neurotransmitter Responses to a Pain Stressor. Science. 2003; 299(5610):1240-1243.
  20. Klepstad P et al. Genetic variability and clinical efficacy of morphine. Acta Anasthesiol Scand. 2005; 49:902-908.
  21. Mannisto PT and S Kaakkola. Catechol-O-methyltransferase (COMT): Biochemistry, Molecular Biology, Pharmacology, and Clinical Efficacy of the New Selective COMT Inhibitors. Pharm Rev. 1999; 51(4):594-622.
  22. Corvol JC et al. The COMT Val158Met polymorphism affects the response to entacapone in Parkinson’s disease: a randomized crossover clinical trial. Ann Neurol. 2011; 69(1):111-118.
  23. Ball P and R Knuppen. Catecholoestrogens (2-and 4-hydroxyoestrogens): chemistry, biogenesis, metabolism, occurrence and physiological significance. Acta Endocrinol. Suppl. 1980; 232:1-127.
  24. Lakhani NJ et al. 2-Methoxyestradiol, a Promising Anticancer Agent. Pharmacotherapy. 2003; 23:165-172.
  25. Lavigne JA et al. The Effects of Catechol-O-Methyltransferase Inhibition on Estrogen Metabolite and Oxidative DNBA Damage Levels in Estradiol-treated MCF-7 Cells. Cancer Research. 2001; 61:7488-7494.
  26. Worda C et al. Influence of the catechol-O-methyltransferase (COMT) codon 158 polymorphism on estrogen levels in women. Human Reproduction. 2003; 18(2):262-266.
  27. Eriksson AL et al. The COMT val158met polymorphism Is Associated with Early Pubertal Development, Height and Cortical Bone Mass in Girls. Pediatr Res. 2005; 58(1):71-77.
  28. Masurier M et al. Effect of Acute Tyrosine Depletion in Using a Branched Chain Amino-Acid Mixture on Dopamine Neurotransmission in the Rat Brain. Neuropsychopharmacology. 2006; 31(2):310-317.
  29. Sarris J et al. S-adenosyl methionine (SAMe) versus escitalopram and placebo in major depression RCT: Efficacy and effects of histamine and carnitine as moderators of response. J Affect Disord. 2014; 164:76-81.
  30. Kennedy D et al. Effects of high-dose B vitamin complex with vitamin C and minerals on subjective mood and performance in healthy males. Psychopharmacology (Berl). 2010; 211(1):55-68.
  31. Li Y et al. Functional and structural comparisons of cysteine residues in the Val108 wild type and Met108 variant of human soluble catechol O-methyltransferase. Chem Biol Interact. 2005; 152(2-3):151-163.
  32. Fava M et al. Rapidity of onset of the antidepressant effect of parenteral S-adenosyl-l-methionine. Psychiatry Res. 1995; 56(3):295-297.
  33. Jeffery DR and JA Roth. Kinetic reaction mechanism for magnesium binding to membrane-bound and soluble catechol O-methyltransferase. Biochem. 1987; 26(10):2955-2958.
  34. Sowa-Kucma M et al. Zinc, magnesium and NMDA receptor alterations in the hippocampus of suicide victims. J Affect Disord. 2013; 151(3):924-931.
  35. Basheer MP et al. A study of serum magnesium, calcium and phosphorus level, and cognition in the elderly population of South India. Alexandria J Med. 2016; 52(4):303-308.
  36. Yary T et al. Dietary magnesium intake and the incidence of depression: A 20 year follow-up study. J Affect Disord. 2016; 193:94-98.
  37. Haan MN et al. Homocysteine, B vitamins, and the incidence of dementia and cognitive impairment: Results from the Sacramento Area Latino Study on Aging. Am J Clin Nutr. 2007; 85(2):511-517.
  38. Smith AD et al. Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: A randomized controlled trial. PLoS One. 2010; 5(9):1-10.
  39. Mitchell ES et al. B vitamin polymorphisms and behavior: Evidence of associations with neurodevelopment, depression, schizophrenia, bipolar disorder and cognitive decline. Neurosci Biobehav Rev. 2014; 47:307-320.
  40. Hiroi T et al. Dopamine formation from tyramine by CYP2D6. Biochem Biophys Res Commun. 1998; 249(3):838-843.
  41. Zhu ZT et al. Tyramine excites rat subthalamic neurons in vitro by a dopamine-dependent mechanism. Neuropharmacology. 2007; 52(4):1169-1178.
  42. Burchett SA et al. The mysterious trace amines: Protean neuromodulators of synaptic transmission in mammalian brain. Prog Neurobiol. 2006; 79:223-246.
  43. Papaleo F et al. Sex-dichotomous effects of functional COMT genetic variations on cognitive functions disappear after menopause in both health and schizophrenia. Eur Neuropsychopharmacol. 2015; 25(12):2349-2363.
  44. Almey A et al. Estrogen receptors in the central nervous system and their implication for dopamine-dependent cognition in females. Horm Behav. 2015; 74:125-138.
  45. McCann S et al. Changes in 2-hydroxyestrone and 16α-hydroxyestrone metabolism with flaxseed consumption: Modification by COMT and CYP1B1 genotype. Cancer Epidemiol Biomarkers Prev. 2007; 16(2):256-262.
  46. Rižner TL. Estrogen biosynthesis, phase I and phase II metabolism, and action in endometrial cancer. Mol Cell Endocrinol. 2013; 381(1-2):124-139.
  47. Masurier M et al. Effect of Acute Tyrosine Depletion in Using a Branched Chain Amino-Acid Mixture on Dopamine Neurotransmission in the Rat Brain. 2006; 31(2):310-317.
  48. Fernstrom HD and MH Fernstrom. Tyrosine, Phenylalanine, and Catecholamine Synthesis and Function in the Brain. J. Nutr. 2007; 137(6):1539S-1547S.
  49. Reus G et al. Kynurenine pathway dysfunction in the pathophysiology and treatment of depression: Evidences from animal and human studies. J Psychiatr Res. 2015; 68:316-328.
  50. Jangid P et al. Comparative study of efficacy of l-5-hydroxytryptophan and fluoxetine in patients presenting with first depressive episode. Asian J Psychiatr. 2013; 6(1):29-34.
  51. Lowe S et al. L-5-Hydroxytryptophan augments the neuroendocrine response to a SSRI. Psychoneuroendocrinology. 2006; 31(4):473-484.
  52. Lardner A et al. Neurobiological effects of the green tea constituent theanine and its potential role in the treatment of psychiatric and neurodegenerative disorders. Nutritional Neuroscience. 2014; 17(4):145-155.
  53. Mu W et al. An overview of biological production of L-theanine. Biotechnol Adv. 2015; 33(3-4):335-342.
  54. Kakuda T. Neuroprotective effects of theanine and its preventive effects on cognitive dysfunction. Pharmacol Res. 2011; 64(2):162-168.
  55. Tian X et al. Protective effect of l-theanine on chronic restraint stress-induced cognitive impairments in mice. Brain Res. 2013; 1503:24-32.
  56. Martínez-Banaclocha M et al. N-acetyl-cysteine in the treatment of Parkinson’s disease. What are we waiting for? Med Hypotheses. 2012; 79(1):8-12.
  57. Dean O. et al. N-acetyl cysteine restores brain glutathione loss in combined 2-cyclohexene-1-one and d-amphetamine-treated rats: Relevance to schizophrenia and bipolar disorder. Neurosci Lett. 2011; 499(3):149-153.
  58. Botsakis K et al. 17β-Estradiol/N-acetylcysteine interaction enhances the neuroprotective effect on dopaminergic neurons in the weaver model of dopamine deficiency. Neuroscience. 2016; 320:221-229.
  59. Tunbridge E et al. Polymorphisms in the catechol‐O‐methyltransferase (COMT) gene influence plasma total homocysteine levels. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 147.6 (2008):996-999.
  60. Paul R and A. Borah. The potential physiological crosstalk and interrelationship between two sovereign endogenous amines, melatonin and homocysteine. Life Sci. 2015; 139:97-107.
  61. Hursel R et al. The Role of Catechol-o-Methyl Transferase Val (108/158) MET Polymorphism (rs4680) in the effect of Green Tea on Resting Energy Expenditure and Fat Oxidation: A Pilot Study. 2014; 9(9): e106220.
  62. Lorenz M et al. The activity of catechol-O-methyltransferase (COMT) is not impaired by high doses of epigallocatechin-3-gallate (EGCG) in vivo. Eur J Pharmacol. 2014; 740: 645-651.
  63. Kang K et al. Beneficial effects of natural phenolics on levodopa methylation and oxidative neurodegeneration. Brain Res. 2013; 1497:1-14.
  64. Kang K et al. Dual beneficial effects of (-)-epigallocatechin-3-gallate on levodopa methylation and hippocampal neurodegeneration: In vitro and in vivo studies. PLoS One. 2010; 5(8): e11951.
  65. Xie X et al. Adenosine and dopamine receptor interactions in striatum and caffeine-induced behavioral activation. Comp Med. 2007; 57(6):538-545.
  66. Witte A et al. COMT Val158Met polymorphism modulates cognitive effects of dietary intervention. Front Aging Neurosci. 2010; 2:146.
  67. Voelcker-Rehage C et al. COMT gene polymorphisms, cognitive performance, and physical fitness in older adults. Psychol Sport Exerc. 2015; 20:20-28.
  68. Zhu BT et al. Effects of tea polyphenols and flavonoids on liver microsomal glucuronidation of estradiol and estrone. J Steroid Biochem Mol Biol. 1998; 64(3-4):207-215.
  69. Moon YJ et al. Dietary flavonoids: Effects on xenobiotic and carcinogen metabolism. Toxicol Vitr. 2006; 20 (2): 187-210.
  70. Ullah N et al. Green tea phytocompounds as anticancer: A review. Asian Pacific J Trop Dis. 2016; 6(4):330-336.

Mood Profile

  1. Lachman H et al. Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders. Pharmacogenetics 1996; 6:243-250.
  2. Weinshilboum R et al. Methylation Pharmacogenetics: Catechol-O methyltransferase, Thiopurine Methyltransferase, and Histamine N-Methyltransferase. Annu. Rev. Pharmacol. Toxicol. 1999; 39:19-52.
  3. Genetics Home Reference. Genes: COMT. http://ghr.nlm.nih.gov/gene/COMT.
  4. Mier D et al. Neural substrates of pleiotropic action of genetic variation in COMT: a meta-analysis. Molecular Psychiatry. 2010; 15:918-927.
  5. Lester K et al. Therapygenetics: Using genetic markers to predict response to psychological treatment for mood and anxiety disorders. Biology of Mood & Anxiety Disorders. 2013; 3:4.
  6. Cheng JB et al. Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25-hydroxylase. Proc Natl Acad Sci U S A. 2004; 101:7711–7715.
  7. Ahn J et al. Genome-wide association study of circulating vitamin D levels. Human Molecular Genetics. 2010; 19(13): 2739-2745.
  8. Nissen J et al. Vitamin D Concentrations in Healthy Danish Children and Adults. PLOS One. 2014; 9(2):e89907.
  9. Harris HW et al. Supplementation might help patients with depression, seasonal mood disturbances. Current Psych. 2013; 12(4):19-25.
  10. Houssein-Nezhad A et al. Vitamin D for Health: A Global Perspective. Mayo Clin. Proc. 2013; 88(7):720-755.
  11. Kelly RJ et al. Sequence and expression of a candidate for the human Secretor blood group alpha (1,2)fucosyltransferase gene (FUT2). Homozygosity for an enzyme-inactivating nonsense mutation commonly correlates with the non-secretor phenotype. J Biol Chem. 1995; 270:4640–4649.
  12. Hazra A et al. Genome-wide significant predictors of metabolites in the one-carbon metabolism pathway. Hum Mol Gen. 2009; 18(23):4677-4687.
  13. Semmes BJ. Depression: a role for omega-3 fish oils and B vitamins? Evid. Based Integr. Med. 2005; 2:229–237.
  14. Tiemeier H et al. Vitamin B12, Folate, and Homocysteine in Depression: The Rotterdam Study. Am J Psychiatry. 2002; 159:2099-2101.
  15. Frankenburg, FR. The role of one-carbon metabolism in schizophrenia and depression. Harv. Rev. Psychiatry. 2007; 15:146–160.
  16. Seppälä et al. Association between vitamin b12 levels and melancholic depressive symptoms: a Finnish population-based study. BMC Psychiatry 2013;13:145.
  17. Tanaka T et al. Genome-wide Association Study of Vitamin B6, Vitamin B12, Folate, and Homocysteine Blood Concentrations. The American Journal of Human Genetics. 2009; 84:477-482.
  18. Gozdzik A et al. Association of vitamin D binding protein (VDBP) polymorphisms and serum 25(OH)D concentrations in a sample of young Canadian adults of different ancestry. J Steroid Biochem Mol Biol. 2011; 127:405–412.
  19. Ahn J et al. Genome-wide association study of circulating vitamin D levels. Human Molecular Genetics. 2010; 19(13) 2739-2745.
  20. Nissen J et al. Vitamin D Concentrations in Healthy Danish Children and Adults. PLOS One. 2014; 9(2):e89907.
  21. Foucan L et al. Polymorphisms in GC and NADSYN1 Genes are associated with vitamin D status and metabolic profile in non-diabetic adults. BMC Endocrine Disorders. 2013; 13:36.
  22. Wang T et al. Common genetic determinants of vitamin D insufficiency: a genome-wide association study. Lancet. 2010; 376(9736):180-188.
  23. Grober U et al. Vitamin D: Update 2013: From rickets prophylaxis to general preventive healthcare. Dermato-Endocrinology. 2013; 5(3):331-47.
  24. Bischoff-Ferrari HA et al. A pooled analysis of vitamin D dose requirements for fracture prevention. N Engl J Med. 2012; 367:40–9.
  25. Bjelland I et al. Folate, Vitamin B12, Homocysteine, and the MTHFR 677CT Polymorphism in Anxiety and Depression: The Hordaland Homocysteine Study. Arch Gen Psychiatry. 2003; 60(6):618-626.
  26. Beydoun MA et al. Serum folate, vitamin B-12 and homocysteine and their association with depressive symptoms among US adults. Psychosom Med. 2010;72(9):862-873.
  27. Refsum H et al. The Hordaland Homocysteine Study: A Community-Based Study of Homocysteine, Its Determinants, and Associations with Disease. J Nutr. 2006; 136:1731S-1740S.
  28. Frosst P et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 1995; 10:111–113.
  29. Lewis SJ et al. The thermolabile variant of MTHFR is associated with depression in the British Women’s Heart and Health Study and a meta-analysis. Molecular Psychiatry. 2006; 11:352-360.
  30. Van der Put NM et al. A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects? Am J Hum Genet. 1998; 62(5):1044–51.
  31. Weisberg I et al. A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Mol Genet Metab. 1998; 64:169–72.
  32. Nurk E et al. Plasma Total Homocysteine and Memory in the Elderly: The Hordaland Homocysteine Study. Ann Neurol. 2005; 58:847-857.
  33. Rajagopalan P et al. Common folate gene variant, MTHFR C677T, is associated with brain structure in two independent cohorts of people with mild cognitive impairment. Neuroimage Clin. 2012; 1(1):179-187. 179-187.
  34. Lewis SJ et al. The thermolabile variant of MTHFR is associated with depression in the British Women’s Heart and Health Study and a meta-analysis. Molecular Psychiatry. 2006; 11:352-360.
  35. Gilbody S et al. Methylenetetrahydrofolate Reductase (MTHFR) Genetic Polymorphisms and Psychiatric Disorders: A HuGE Review. Am J Epidemiol. 2007;165:1-13.

MTHFR

  1. Van der Put NM et al. A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects? Am J Hum Genet. 1998; 62(5):1044–51.
  2. Wagner C. Biochemical role of folate in cellular metabolism. In: Bailey LB, editor. Folate in health and disease. New York, NY: Marcel Dekker Inc.; 1995. p. 23–42.
  3. Bailey LB and JF Gregory III. Polymorphisms of Methylenetetrahydrofolate Reductase and Other Enzymes: Metabolic Significance, Risks and Impact on Folate Requirement. J Nutr. 1999; 129(5):919-22.
  4. Stover PJ. Polymorphisms in 1-Carbon Metabolism, Epigenetics and Folate-Related Pathologies. J. Nutrigenet Nutrigenomics. 2012; 4(5):293-305.
  5. Refsum H et al. The Hordaland Homocysteine Study: A Community-Based Study of Homocysteine, Its Determinants, and Associations with Disease. J Nutr. 2006; 136:1731S-1740S.
  6. Frosst P et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 1995; 10:111–113.
  7. Weisberg I et al. A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Mol Genet Metab. 1998; 64:169–72.
  8. Teng Z. The 677C>T (rs1801133) polymorphism in the MTHFR gene contributes to colorectal cancer risk: a meta-analysis based on 71 research studies. PLoS One. 2013; 8(2):e55332.
  9. Yang L, et al. Impact of methylenetetrahydrofolate reductase (MTHFR) polymorphisms on methotrexate-induced toxicities in acute lymphoblastic leukemia: a meta-analysis. Tumor Biol. 2012; 33(5):1445–54.
  10. Bjelland I et al. Folate, Vitamin B12, Homocysteine, and the MTHFR 677CT Polymorphism in Anxiety and Depression: The Hordaland Homocysteine Study. Arch Gen Psychiatry. 2003; 60(6):618-626.
  11. Beydoun MA et al. Serum folate, vitamin B-12 and homocysteine and their association with depressive symptoms among US adults. Psychosom Med. 2010; 72(9):862-873.
  12. Nurk E et al. Plasma Total Homocysteine and Memory in the Elderly: The Hordaland Homocysteine Study. Ann Neurol. 2005; 58:847-857.
  13. Rajagopalan P et al. Common folate gene variant, MTHFR C677T, is associated with brain structure in two independent cohorts of people with mild cognitive impairment. Neuroimage Clin. 2012; 1(1):179-187. 179-187.
  14. Cotlarciuc I et al. Effect of genetic variants associated with plasma homocysteine levels on stroke risk. Stroke. 2014; 45(7):1920-4.
  15. Refsum H et al. The Hordaland Homocysteine Study: A community- based study of homocysteine, its determinants, and associations with disease. The Journal of Nutrition. 2006; 136:1731S-1740S.
  16. Simpson J et al. Micronutrients and women of reproductive potential: required dietary intake and consequences of dietary deficiency or excess. Part I – Folate, Vitamin B12, Vitamin B6. J Matern Fetal Neonatal Med. 2011; 24(1):1-24.
  17. NIH: Office of Dietary Supplements. Folate. http://ods.od.nih.gov/factsheets/Folate-HealthProfessional/
  18. Pietrzrik K. Folic acid and L-5-Methyltetrahydrofolate: Comparison of Clinical Pharmacokinetics and Pharmacodynamics. Cln Pharmacokinet. 2010; 49(8):535-548.
  19. Jain R et al. Beyond the resistance: how novel neurobiological understandings of depression may lead to advanced treatment strategies. J Clin Psychiatry. 2012; 73(11):e30.
  20. Soleimani A et al. Comparison of oral folic acid and folinic acid on blood homocysteine level of patients on hemodialysis. Iran J Kidney Dis. 2011: 5(1):45-9.
  21. Chen Z et al. Purification and Kinetic Mechanism of a Mammalian Methionine Synthase from Pig Liver. J Biol Chem. 1994; 269(44):27193-27197.
  22. Ho G et al. Methylenetetrahydrofolate Reductase Polymorphisms and Homocysteine-Lowering Effect of Vitamin Therapy in Singaporean Stroke Patients. Stroke. 2006; 37:456-460.
  23. Chen X et al. Contrasting behaviors of mutant cystathionine beta-synthase enzymes associated with pyridoxine response. Hum Mutat. 2006; 275(5):474-482.
  24. Dell’Edera D et al. Effect of multivitamins on plasma homocysteine in patients with the 5,10 methylenetetrahydrofolate reductase C677T homozygous state. Molecular Medicine Reports. 2013; 8:609-612.
  25. Betaine: Drug Information. http://www.uptodate.com/contents/betaine-drug-information?source=search_result&search=betaine&selectedTitle=1~9
  26. Lawson-Yuen A eta l. The use of betaine in treatment of elevated homocysteine. Mol Genet Metab. 2006; 88(3):201-207.
  27. Hultberg B et al. Plasma homocysteine and thiol compound fractions after oral administration of N-acetylcysteine. Scand J Clin Lab Invest. 1994; 54:417–422.

Nutritional Health

  1. Ferrucci L et al. “Common Variation in the B-Carotene 15, 15’-Monooxygenase 1 Gene Affects Circulating Levels of Carotenoids: A Genome-wide Association Study.” The American Journal of Human Genetics. 2009; 84, 123-133.
  2. Borel P et al. “Genetic Variations Involved in Interindividual Variability in Carotenoid Status.” Mol Nutr Food Res. 2012; 56(2): 228-40.
  3. Wyss A et al. Expression pattern and localization of β,β-carotene 15,15′-dioxygenase in different tissues. Biochem. J. 2001; 354:521–529.
  4. Lietz G et al. “Single Nucleotide Polymorphisms Upstream from the B-Carotene 15, 15’-Monoxygenase Gene Influence Provitamin A Conversion Efficiency in Female Volunteers.” J. Nutr. 2012; 142(1):161S-165S.
  5. Cheng JB et al. Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25-hydroxylase. Proc Natl Acad Sci U S A. 2004; 101:7711–7715.
  6. Ahn J et al. Genome-wide association study of circulating vitamin D levels. Human Molecular Genetics. 2010; 19(13): 2739-2745.
  7. Nissen J et al. Vitamin D Concentrations in Healthy Danish Children and Adults. PLOS One. 2014; 9(2):e89907.
  8. Harris HW et al. Supplementation might help patients with depression, seasonal mood disturbances. Current Psych. 2013; 12(4):19-25.
  9. Houssein-Nezhad A et al. Vitamin D for Health: A Global Perspective. Mayo Clin. Proc. 2013; 88(7):720-755.
  10. Holick MF and M Garabedian. Vitamin D: photobiology, metabolism, mechanism of action, and clinical applications. In: Favus MJ, ed. Primer on the metabolic bone diseases and disorders of mineral metabolism. 6th ed. Washington, DC: American Society for Bone and Mineral Research. 2006; 129-137.
  11. Lips P and NM van Schoor. The effect of vitamin D on bone and osteoporosis. Best Pract Res Clin Endocrinol Metab. 2011; 25:585–591.
  12. Wang T et al. Common genetic determinants of vitamin D insufficiency: a genome-wide association study. Lancet. 2010; 376(9736):180-188.
  13. Bischoff-Ferrari HA et al. A pooled analysis of vitamin D dose requirements for fracture prevention. N Engl J Med. 2012; 367:40–9.
  14. Grober U et al. Vitamin D: Update 2013: From rickets prophylaxis to general preventive healthcare. Dermato-Endocrinology. 2013; 5(3):331-47.
  15. Kelly RJ et al. Sequence and expression of a candidate for the human Secretor blood group alpha (1,2)fucosyltransferase gene (FUT2). Homozygosity for an enzyme-inactivating nonsense mutation commonly correlates with the non-secretor phenotype. J Biol Chem. 1995; 270:4640–4649.
  16. Hazra A et al. Genome-wide significant predictors of metabolites in the one-carbon metabolism pathway. Hum Mol Gen. 2009; 18(23):4677-4687.
  17. Semmes BJ. Depression: a role for omega-3 fish oils and B vitamins? Evid. Based Integr. Med. 2005; 2:229–237.
  18. Tiemeier H et al. Vitamin B12, Folate, and Homocysteine in Depression: The Rotterdam Study. Am J Psychiatry. 2002; 159:2099-2101.
  19. Frankenburg, FR. The role of one-carbon metabolism in schizophrenia and depression. Harv. Rev. Psychiatry. 2007; 15:146–160.
  20. Seppälä et al. Association between vitamin b12 levels and melancholic depressive symptoms: a Finnish population-based study. BMC Psychiatry 2013; 13:145.
  21. Tanaka T et al. Genome-wide Association Study of Vitamin B6, Vitamin B12, Folate, and Homocysteine Blood Concentrations. The American Journal of Human Genetics. 2009; 84:477-482.
  22. Hazra A et al. Common variants of FUT2 are associated with plasma vitamin B12 levels. Nat. Genet. 2008; 40:1160–1162.
  23. http://lpi.oregonstate.edu/infocenter/vitamins/vitaminB12/.
  24. Gozdzik A et al. Association of vitamin D binding protein (VDBP) polymorphisms and serum 25(OH)D concentrations in a sample of young Canadian adults of different ancestry. J Steroid Biochem Mol Biol. 2011; 127:405–412.
  25. Ahn J et al. Genome-wide association study of circulating vitamin D levels. Human Molecular Genetics. 2010; 19(13) 2739-2745.
  26. Nissen J et al. Vitamin D Concentrations in Healthy Danish Children and Adults. PLoS One. 2014; 9(2):e89907.
  27. Foucan L et al. Polymorphisms in GC and NADSYN1 Genes are associated with vitamin D status and metabolic profile in non-diabetic adults. BMC Endocrine Disorders. 2013; 13:36.
  28. Wang T et al. Common genetic determinants of vitamin D insufficiency: a genome-wide association study. Lancet. 2010; 376(9736):180-188.
  29. Grober U et al. Vitamin D: Update 2013: From rickets prophylaxis to general preventive healthcare. Dermato-Endocrinology. 2013; 5(3):331-47.
  30. Bischoff-Ferrari HA et al. A pooled analysis of vitamin D dose requirements for fracture prevention. N Engl J Med. 2012; 367:40–9.
  31. Wagner C. Biochemical role of folate in cellular metabolism. In: Bailey LB, editor. Folate in health and disease. New York, NY: Marcel Dekker Inc.; 1995. p. 23–42.
  32. Bailey LB and JF Gregory III. Polymorphisms of Methylenetetrahydrofolate Reductase and Other Enzymes: Metabolic Significance, Risks and Impact on Folate Requirement. J Nutr. 1999; 129(5):919-22.
  33. Stover PJ. Polymorphisms in 1-Carbon Metabolism, Epigenetics and Folate-Related Pathologies. J. Nutrigenet Nutrigenomics. 2012; 4(5):293-305.
  34. Refsum H et al. The Hordaland Homocysteine Study: A Community-Based Study of Homocysteine, Its Determinants, and Associations with Disease. J Nutr. 2006; 136:1731S-1740S.
  35. Frosst P et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 1995; 10:111–113.
  36. Van der Put NM et al. A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects? Am J Hum Genet. 1998; 62(5):1044–51.
  37. Weisberg I et al. A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Mol Genet Metab. 1998; 64:169–72.
  38. Teng Z. The 677C>T (rs1801133) polymorphism in the MTHFR gene contributes to colorectal cancer risk: a meta-analysis based on 71 research studies. PLoS One. 2013; 8(2):e55332.
  39. Hara N et al. Molecular identification of human glutamine- and ammonia-dependent NAD synthetases. Carbon-nitrogen hydrolase domain confers glutamine dependency. J. Biol. Chem. 2003; 278(13):10914-10921.
  40. Wassif CA et al. Mutations in the human sterol Δ7-reductase gene at 11q12–13 cause Smith–Lemli–Opitz syndrome. Am. J. Hum. Genet. 1998; 63:55–62.
  41. Wang T et al. Common genetic determinants of vitamin D insufficiency: a genome-wide association study. Lancet. 2010; 376(9736):180-188.
  42. Harris HW et al. Supplementation might help patients with depression, seasonal mood disturbances. Current Psych. 2013; 12(4):19-25.
  43. Houssein-Nezhad A et al. Vitamin D for Health: A Global Perspective. Mayo Clinic. Proc. 2013; 88(7):720-755.
  44. Bischoff-Ferrari HA et al. A pooled analysis of vitamin D dose requirements for fracture prevention. N Engl J Med. 2012; 367:40–9.
  45. Grober U et al. Vitamin D: Update 2013: From rickets prophylaxis to general preventive healthcare. Dermato-Endocrinology. 2013; 5(3):331-47.
  46. Stoltzfus RJ. Iron deficiency: global prevalence and consequences. Food Nutrition Bulletin. 2003; 24:S99–S103.
  47. Patel KV. “Variability and heritability of hemoglobin concentration: an opportunity to improve understanding of anemia in older adults.” Haematologica 2008; 93:1281-1283.
  48. Benyamin B et al. Common variants in TMPRSS6 are associated with iron status and erythrocyte volume. Nature Genetics 2009; 41:1173-1175.
  49. Chambers JC et al. Genome-wide association study identifies variants in TMPRSS6 associated with hemoglobin levels. Nature Genetics 2009; 41:1170-1172.
  50. Morris HA. Vitamin D Activities for Health Outcomes. Ann Lab Med 2014; 34:181-186.
  51. Turner AG. Vitamin D and bone health. Scand J Clin Lab Invest Suppl. 2012; 243:65-72.
  52. Palomba S et al. BsmI vitamin D receptor genotypes influence the efficacy of antiresorptive treatments in postmenopausal osteoporotic women. A 1-year multicenter, randomized and controlled trial. Osteoporosis Int. 2005; 16(8):943-52.
  53. Jia F et al. Vitamin D receptor BsmI polymorphism and osteoporosis risk: a meta-analysis from 26 studies. Genet Test Mol Biomarkers. 2013; 17(1):30-4.
  54. Ji GR. BsmI, TaqI, ApaI and FokI polymorphisms in the vitamin D receptor (VDR) gene and risk of fracture in Caucasians: a meta-analysis. Bone. 2010; 47(3):681-6.
  55. Bischoff-Ferrari HA et al. A pooled analysis of vitamin D dose requirements for fracture prevention. N Engl J Med. 2012; 367:40–9.
  56. Grober U et al. Vitamin D: Update 2013: From rickets prophylaxis to general preventive healthcare. Dermato-Endocrinology. 2013; 5(3):331-47.

PGx Comprehensive

  1. Bloom D et al. The Global Economic Burden of Non-Communicable Diseases. Geneva: World Economic Forum. 2011:1-48.
  2. Ganesh SK et al. Genetics and genomics for the prevention and treatment of cardiovascular disease: update: a scientific statement from the American Heart Association. Circulation. 2013; 128(25):2813-51.
  3. Haddad PM et al. Nonadherence with antipsychotic medication in schizophrenia: challenges and management strategies. Patient Relat Outcome Meas. 2014; 5:43-62.
  4. Hicks JK et al. Clinical Pharmacogenetics Implementation Consortium guideline for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants. Clin Pharmacol Ther. 2013; 93(5):402-8.
  5. Janicki PK. Comprehensive Treatment of Chronic Pain by Medical, Interventional, and Integrative Approaches. Deer TR et al. eds. 2013.
  6. Jannetto PJ and Bratanow NC. Pharmacogenomic considerations in the opioid management of pain. Genome Med. 2010; 2:66.
  7. Johnson J et al. Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C9 and VKORC1 genotypes and warfarin dosing. Clin Pharmacol Ther. 2011; 90(4):625-9.
  8. Johnson JA et al. Institutional profile: University of Florida and Shands Hospital Personalized Medicine Program: clinical implementation of pharmacogenetics. Pharmacogenomics. 2013; 14(7):723-6.
  9. Kelly K et al. Toward achieving optimal response: understanding and managing antidepressant side effects. Dialogues Clin Neurosci. 2008;10(4):409-18.
  10. Kitzmiller JP et al. Pharmacogenomic testing: relevance in medical practice: why drugs work in some patients but not in others. Cleve Clin J Med. 2011; 78(4):243-57.
  11. Kitzmiller JP et al. Statin pharmacogenomics: pursuing biomarkers for predicting clinical outcomes. Discov Med. 2013; 16(86):45-51.
  12. Lamba J et al. PharmGKB summary: very important pharmacogene information for CYP3A5. Pharmacogenet Genomics 2012; 22(7):555-8.
  13. Link E et al. SLCO1B1 variants and statin-induced myopathy–a genomewide study. N Engl J Med. 2008; 359(8):789-99.
  14. McNulty H et al. Homocysteine, B-vitamins and CVD. Proc Nutr Soc. 2008; 67(2):232-7.
  15. Miranda-Massari JR et al. Metabolic Correction in the Management of Diabetic Peripheral Neuropathy: Improving Clinical Results Beyond Symptom Control. Curr Clin Pharmacol. 2011; 6(4):260-273.
  16. Phillips KA et al. Potential Role of Pharmacogenomics in Reducing Adverse Drug Reactions. JAMA. 2001; 286(18):2270.
  17. Ramsey LB et al. The clinical pharmacogenetics implementation consortium guideline for SLCO1B1 and simvastatin-induced myopathy: 2014 update. Clin Pharmacol Ther. 2014; 96(4):423-8.
  18. Refsum H et al. The Hordaland Homocysteine Study: A Community-Based Study of Homocysteine, Its Determinants, and Associations with disease. J Nutr. 2006; 136:1731S-1740S.
  19. Rush AJ et al. Acute and Longer-Term Outcomes in Depressed Outpatients Requiring One or Several Treatment Steps: A STAR*D Report. 2006; 163:1905-1917.
  20. Sadhasivam S and Chidambaran V. Pharmacogenomics of opioids and perioperative pain management. Pharmacogenomics. 2012; 13(15):1719-40.
  21. Samer CF et al. Applications of CYP450 testing in the clinical setting. Mol Diagn Ther. 2013; 17(3):165-84.
  22. Scott S et al. Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450-2C19 (CYP2C19) genotype and clopidogrel therapy. Clin Pharmacol Ther. 2011; 90(2):328-332.
  23. Shaheen K et al. Factor V Leiden: how great is the risk of venous thromboembolism? Cleve Clin J Med. 2012; 79(4):265-72.
  24. Sim SC et al. Pharmacogenomics of drug-metabolizing enzymes: a recent update on clinical implications and endogenous effects. Pharmacogenomics J. 2013; 13(1):1-11.
  25. Tomaszewski M et al. Statin-induced myopathies. Pharmacol Rep. 2011; 63(4):859-866.
  26. Trescot AM and Faynboym S. A Review of the Role of Genetic Testing in Pain Medicine. Pain Physician. 2014; 17:425-445.
  27. U.S. Food and Drug Administration. Table of Pharmacogenomic Biomarkers in Drug Labeling. 08/18/2014. Available at: http://www.fda.gov/drugs/scienceresearch/researchareas/pharmacogenetics/ucm083378.htm.
  28. Van Driest SL et al. Clinically actionable genotypes among 10,000 patients with preemptive pharmacogenomic testing. Clin Pharmacol Ther. 2014; 95(4):423-31.
  29. Varga E and Moll S. Prothrombin 20210 mutation (factor II mutation). Circulation. 2004; 110:e15-8.
  30. Velligan DI et al. The expert consensus guideline series: adherence problems in patients with serious and persistent mental illness. J Clin Psychiatry. 2009; 70 Suppl 4:1-46; quiz 47-8.
  31. Voora D and Ginsburg GS. Clinical application of cardiovascular pharmacogenetics. J Am Coll Cardiol. 2012; 60(1):9-20.
  32. Xu Y and Johnson A. Opioid therapy pharmacogenomics for noncancer pain: efficacy, adverse events, and costs. Pain Res Treat. 2013; 2013:943014.
  33. Zandi PP and Judy JT. The Promise and Reality of Pharmacogenetics in Psychiatry. Psychiatr Clin North Am. 2010;33(1):181-224.

Weight Management

  1. Martínez JA et al. Obesity risk is associated with carbohydrate intake in women with the Gln27Glu β2-adrenoreceptor polymorphism. J Nutr. 2003; 133:2549-2554.
  2. Large V et al. Human Beta-2 adrenoreceptor gene polymorphisms are highly frequent in obesity and associate with altered adipocyte Beta-2 adrenoceptor function. J Clin Invest. 1997; 100:3005-3013.
  3. Macho-Azcarate et al. Gln27Glu polymorphism in the beta2 adrenergic receptor gene and lipid metabolism during exercise in obese women. Int J Obesity. 2002; 26:1434-1441.
  4. HGNC. http://www.genenames.org/cgibin/gene_symbol_report? hgnc_id=HGNC:286.
  5. org. Nutrition and Healthy Eating: Carbohydrates: How carbs fit into a healthy diet. http://www.mayoclinic.org/healthy-living/nutrition-and-healthy-eating/in-depth/carbohydrates/art-20045705?pg=1.
  6. Layman DK. Dietary Guidelines should reflect new understandings about adult protein needs. Nutr Metab (Lond). 2009; 6:12.
  7. Phares DA et al. Association Between Body Fat Response to Exercise Training and Multilocus ADR Genotypes. Obes Res. 2004; 12(5):807-815.
  8. Corbalan MS et al. The 27Glu polymorphism of the Beta2-adrenergic receptor gene interacts with physical activity influencing obesity risk among female subjects. Clin Genet. 2002; 61:305-307.
  9. Zhang et al. Association of Gln27Glu and Arg16Gly Polymorphisms in Beta2-Adrenergic Receptor Gene with Obesity Susceptibility: A Meta-Analysis. PLoS ONE. 2014; 9(6): e100489.
  10. Levy E et al. The polymorphism at codon 54 of the FABP2 gene increases fat absorption in human intestinal explants. J Biol Chem. 2001; 276:39679-39684.
  11. Marin C et al. The Ala54Thr polymorphism of the fatty acid-binding protein 2 gene is associated with a change in insulin sensitivity after a change in the type of dietary fat. Am J Clin Nutr. 2005; 82:196-200.
  12. Albala C et al. FABP2 Ala54Thr polymorphism and diabetes in Chilean elders. Diab Res Clin Pract. 2007; 77:245-250.
  13. Paglialunga S et al. Regulation of postprandial lipemia: an update on current trends. Appl Physiol Nutr Metab. 2007; 32:61-75.
  14. Takakura Y et al. Thr54 allele of the FABP2 gene affects resting metabolic rate and visceral obesity. Diabetes Res Clin Pract. 2005; 67:36-42.
  15. Hegele RA. A Review of Intestinal Fatty Acid Binding Protein Gene Variation and the Plasma Lipoprotein Response to Dietary Components. Clin Biochem. 1998; 31:609-612.
  16. Gaggini M et al. Non-Alcoholic Fatty Liver Disease (NAFLD) and Its Connection with Insulin Resistance, Dyslipidemia, Atherosclerosis and Coronary Heart Disease. Nutrients. 2013; 5:1544-1560.
  17. Almeida JC et al. The Ala54Thr polymorphism of the FABP2 gene influences the postprandial fatty acids in patients with type 2 diabetes. J Clin Endocrin Met. 2010; 95:3909-3917.
  18. Dworatzek PD et al. Postprandial lipemia in subjects with the threonine 54 variant of the fatty acid-binding protein 2 gene is dependent on the type of fat ingested. Am J Clin Nutr. 2004; 79:1110-1117.
  19. Weiss EP et al. FABP2 Ala54Thr genotype is associated with glucoregulatory function and lipid oxidation after a high-fat meal in sedentary nondiabetic men and women. Am J Clin Nutr. 2007; 85:102-108.
  20. Weickert MO et al. Metabolic Effects of Dietary Fiber consumption and Prevention of Diabetes. J Nutr. 2008; 138(3):439-442.
  21. org. Nutrition and Healthy Eating: Carbohydrates: How carbs fit into a healthy diet. http://www.mayoclinic.org/ healthy-living/nutrition-and-healthy-eating/in-depth/carbohydrates/ art-20045705?pg=1
  22. Pfeiffer M et al. The influence of walking performed immediately before meals with moderate fat content on postprandial lipemia. Lipids Health Dis. 2005; 4:24.
  23. Brandou F et al. Impact of high- and low-intensity targeted exercise training on the type of substrate utilization in obese boys submitted to a hypocaloric diet. Diabetes Metab. 2005; 31(4 Pt 1):327-325.
  24. Corella D et al. A High Intake of Saturated Fatty Acids Strengthens the Association between the Fat Mass and Obesity-Associated Gene and BMI. J of Nutr. 2011; 141:2219-2225.
  25. Kilpelainen TO et al. Physical Activity Attenuates the Influence of FTO Variants on Obesity Risk: A Meta-Analysis of 218,166 Adults and 19.268 Children. PLOS Medicine. 2011; 8(11):31001116.
  26. Frayling TM et al. A Common Variant in the FTO Gene is Associated with Body Mass Index and Predisposition to Childhood and Adult Obesity. Science. 2007; 316(58):889-894.
  27. Berulava T and Horsthemke B. The obesity-associated SNPs in intron 1 of the FTO gene affect primary transcript levels. Eur J Hum Genet. 2010; 18(9):1054-1058.
  28. Karra E et al. A link between FTO, ghrelin, and impaired brain food-cue responsivity. J Clin Invest. 2013; 123(8):3539-3551.
  29. Lu Y et al. Obesity genomics: assessing the transferability of susceptibility loci across diverse populations. Genome Med. 2013; 5:55.
  30. Cho YS et al. A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits. Nat Genet. 2009; 41:527-534.
  31. Jaaskelainen A et al. Meal Frequencies Modify the Effect of Common Genetic Variants on Body Mass Index in Adolescents of the Northern Finland Birth Cohort 1986. PLOS One. 2013; 8(9):e73802.
  32. Zhang X et al. FTO Genotype and 2-Year Change in Body Composition and Fat Distribution in Response to Weight-Loss Diets: The POUNDS Lost Trial. Diabetes. 2012; 61:3005-3011.
  33. Ortega-Azorin C et al. Associations of the FTO rs9939609 and the MC4R rs17782313 polymorphisms with type 2 diabetes are modulated by diet, being higher when adherence to the Mediterranean diet pattern is low. Cardiovasc Diabetol. 2012; 11:137.
  34. Mitchell JA et al. FTO Genotype and the Weight Loss Benefits of Moderate Intensity Exercise. Obesity. 2010; 18(3):641-643.
  35. Lauria F et al. Prospective Analysis of the Association of a Common Variant of FTO (rs9939609) with Adiposity in Children: Results of the IDEFICS Study. PLoS One. 2012; 7: e48876.
  36. Velders FP et al. FTO at rs9939609, food responsiveness, emotional control and symptoms of ADHD in preschool children. PLoS One. 2012; 7:e49131.
  37. Wardle J et al. Obesity associated genetic variation in FTO is associated with diminished satiety. J Clin Endocrinol Metab. 2008; 93:3640–3643.
  38. den Hoed M et al. Postprandial responses in hunger and satiety are associated with the rs9939609 single nucleotide polymorphism in FTO. Am J Clin Nutr. 2009; 90:1426–1432.
  39. Loos RJF et al. Common variants near MC4R are associated with fat mass, weight and risk of obesity. Nat Genet. 2008; 40(6):768-775.
  40. Qi L et al. The common obesity variant near MC4R gene is associated with higher intakes of total energy and dietary fat, weight change and diabetes risk in women. Human Mol Genetics 2008; 17:3502-3508.
  41. Xi B et al. Common polymorphism near the MC4R gene is associated with type 2 diabetes: data from a meta-analysis of 123,373 individuals. Diabetologia 2012; 55:2660–2666.
  42. Stutzmann F et al. Common genetic variation near MC4R is associated with eating behaviour patterns in European populations. Int J Obes. 2009; 33:373-378.
  43. Xi B et al. Influence of physical inactivity on associations between single nucleotide polymorphisms and genetic predisposition to childhood obesity. Am J Epidemiology 2011; 173:1256-1262.
  44. Acosta A et al. Association of melanocortin 4 receptor gene variation with satiation and gastric emptying in overweight and obese adults. Genes Nutr. 2014; 9(2):384.
  45. Zlatohlavek L et al. FTO and MC4R gene variants determine BMI changes in children after intensive lifestyle intervention. Clin Biochem. 2013; 46:313-31.
  46. Raynor HA et al. Dietary energy density and successful weight loss maintenance. Eat Behav. 2011; 12(2):119-125.
  47. Otten JJ et al. DRI: Dietary Reference Intakes: The Essential Guide to Nutrient Requirements. Washington, DC. National Academies Press. c2006.
  48. OSU: Linus Pauling Institute. Glycemic Index and Glycemic Load. http://lpi.oregonstate.edu/infocenter/foods/grains/gigl.html
  49. Jaaskelainen A et al. Meal Frequencies Modify the Effect of Common Genetic Variants on Body Mass Index in Adolescents of the Northern Finland Birth Cohort 1986. PLOS One. 2013; 8(9):e73802.
  50. Little JP et al. A practical model of low-volume high-intensity interval training induces mitochondrial biogenesis in human skeletal muscle: potential mechanisms. J Physiol. 2010; 588 (Pt 6):1011-1022.
  51. Bauer F et al. Obesity genes identified in genome-wide association studies are associated with adiposity measures and potentially with nutrient-specific food preference. Am J Clin Nutr. 2009; 90:951–959.
  52. Volckmar AL et al. Mutation screen in the GWAS derived obesity gene SH2B1 including functional analyses of detected variants. BMC Med Genomics. 2012; 5:65.
  53. Jamshidi Y et al. The SH2B gene is associated with serum leptin and body fat in normal female twins. Obesity. 2007; 15:5-9.
  54. Ren D et al. Neuronal SH2B1 is essential for controlling energy and glucose homeostasis. J Clin Invest. 2007; 117:397–406.
  55. Morris DL et al. SH2B1 enhances insulin sensitivity by both stimulating the insulin receptor and inhibiting tyrosine dephosphorylation of insulin receptor substrate proteins. Diabetes. 2009; 58:2039-2047.
  56. McCaffery JM et al. Obesity susceptibility loci and dietary intake in the Look AHEAD Trial. Am J Clin Nutr. 2012; 95:1477-1486.
  57. Duan C et al. Disruption of the SH2-B gene causes age-dependent insulin resistance and glucose intolerance. Mol Cell Biol 2004; 24:7435–7443.
  58. Ren D et al. Identification of SH2-B as a key regulator of leptin sensitivity, energy balance, and body weight in mice. Cell Metabolism. 2005; 2:95–104.
  59. Wolpert HA et al. Dietary Fat Acutely Increases Glucose Concentrations and Insulin Requirements in Patients With Type 1 Diabetes: Implications for carbohydrate-based bolus dose calculation and intensive diabetes management. Diabetes Care. 2012; 36(4):810-816.
  60. Diabetes.org American Diabetes Association: Insulin Basics. http://www.diabetes.org/living-with-diabetes/treatment-and-care/ medication/insulin/insulin-basics.html.
  61. Klok MD et al. The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review. Obes Rev. 2007; 8(1):21-34.
  62. Bachman JL et al. Eating frequency is higher in weight loss maintainers and normal-weight individuals than in overweight individuals. J Am Diet Assoc. 2011; 111(11):1730-4.
  63. Lichtenstein MB et al. Exercise Addiction in Men Is Associated With Lower Fat-Adjusted Leptin Levels. Clin J Sport Med. 2015; 25(2):138-43.
  64. OSU: Linus Pauling Institute. Glycemic Index and Glycemic Load. http://lpi.oregonstate.edu/infocenter/foods/grains/gigl.html
  65. Zhang Z et al. A high-legume low-glycemic index diet reduces fasting plasma leptin in middle-aged insulin-resistant and –sensitive men. Eur J Clin Nutr. 2011; 65(3):415-418.
  66. Fall T et al. The role of obesity-related genetic loci in insulin sensitivity. Diabet Med. 2012; 29(7):e62-66.
  67. Robiou-du-Pont S et al. Contribution of 24 obesity-associated genetic variants to insulin resistance, pancreatic beta-cell function and type 2 diabetes. Int J Obesity. 2013; 37:980-985.
  68. Weickert MO et al. Metabolic Effects of Dietary Fiber Consumption and Prevention of Diabetes. J Nutr. 2008; 138(3):439-442.
  69. Willett WC. Eat, Drink, and be Healthy: The Harvard Medical School Guide to Healthy Eating. New York: Simon & Schuster; 2001.
  70. Zaccaria M et al. Plasma leptin and energy expenditure during prolonged, moderate intensity, treadmill exercise. J Endocrinol Invest. 2013; 36(6):396-401.
  71. Li S et al. Physical Activity Attenuates the Genetic Predisposition to Obesity in 20,000 Men and Women from EPIC-Norfolk Prospective Population Study. PLOS Medicine. 2010; 7(8):e1000332.
  72. Lee S et al. Aerobic exercise but not resistance exercise reduces intrahepatic lipid content and visceral fat and improves insulin sensitivity in obese adolescent girls: a randomized controlled trial. Am J Physiol Endocrinol Metab. 2013; 305(10):E1222-1229.

Please contact Kashi Health for further scientific reference papers.