Genetics and Cardiovascular Disease Current research strongly indicates that an elevated level of homocysteine in the blood (hyperhomocysteinemia) is an independent risk factor for cardiovascular disease. Early-onset coronary artery disease is more common in patients under age 50 with high homocysteine levels. It has been shown that excess homocysteine damages the epithelial lining of blood vessels, leading to the development of plaque in our arteries. Over time, this causes blockages in blood circulation and can result in heart attack or stroke. This damage to blood vessels is also responsible for starting reactions that can trigger sudden cardiovascular attacks like myocardial infarction, thrombotic stroke or deep-venous thrombosis. In addition, kidney complications and renal failure have been closely tied with high plasma homocysteine levels. The efficiency of this metabolic process is reliant on folate and other B vitamins (riboflavin, B12, B6) from our diet. A low intake of folate has been linked to hyperhomocysteinemia (high homocysteine levels) and associated diseases. Additionally, the cause of hyperhomocysteinemia has been linked to genetic factors. The MTHFR (methyltetrahydrofolate reductase) gene is involved in folate metabolism and is needed for the proper conversion of homocysteine to methionine, so this enzyme reduces homocysteine levels. People who have variations (polymorphisms) of this gene produce a defective converting enzyme. They are more likely to develop hyperhomocysterina and have increased risk of heart disease; defective MTHFR variations are prevalent in 20-50% of the population. As well as being involved in homocysteine metabolism, folate is also involved in DNA synthesis and repair. When dietary folate levels are too low or the MTHFR enzyme is defective, the wrong DNA molecules are made; this leads to unstable DNA, which is more vulnerable to disease. Many studies have shown mothers with the MTHFR genetic defect have a higher chance of giving birth to infants with neural tube defects. Other pregnancy complications like repeated miscarriages and Down’s syndrome have also been linked to variations of this gene. This particular gene have also been linked to an increased risk of cervical, breast, and esophageal cancers due to increased homocysteine damaging epithelial cells. While polymorphisms in our MTHFR gene are unavoidable, you can reduce your risk of negative health effects from it by using the correct diet and nutritional supplements. Many studies have indicated supplementation with folate and other B vitamins lowers homocysteine levels in those with a defective MTHFR enzyme. By balancing the levels of methionine with homocysteine, endothelial factors are protected. The vasoprotective effects of B vitamin supplementation could then reduce the risk of developing the dangerous conditions associated with high homocysteine levels. Unfortunately, the foods we eat lose the majority of their vitamin B during cooking and processing. Also, as we age, our ability to absorb folate from our foods decreases. The processing of wheat into white flour removes 68% of the folate content, only 25-50% of folate in foods is biologically available and our diets do not provide the recommended 400 micrograms of folate a day. Additionally, alcohol consumption can deplete already badly need B vitamins. These factors can be more serious for people with MTHFR genetic variations as they are more likely to have deficiencies, making supplementation even more important. Genetic testing for nutritional metabolism genes such as the MTHFR gene can help to direct your diet and supplement plan in the right direction. By taking a genetic test you can determine if you need to be extra concerned about folate and B vitamin use, heart disease or DNA repair. By adapting your diet and supplement regime to your genetics you can be ensured that you are doing what is right for your body and increase your chances of living a long, healthy life. Tamsin Pitcher is the Director of Nutritional Services at One Person Health Inc., the first company to develop personalized and custom manufactured health solutions based on genetic testing. For additional information feel free to contact her at [email protected] or visit the One Person Health website at www.onepersonhealth.com. REFERENCES Ashfield-Watt PA, et al. (Jul, 2002). Methylenetetrahydrofolate reductase 677CàT genotype modulates homocysteine responses to a folate-rich diet or a low-dose folic acid supplement: A randomized controlled trial. American Journal of Clinical Nutrition. 76(1)180-6. Aubard Y, Darodes N, Cantaloube M. (2000). Hyperhomocysteinemia and pregnancy— review of our present understanding and therapeutic implications. European Journal of Obstetrics, Gynecology, and Reproductive Biology. Dec, 58(6 Suppl): 443-7. Bailey LB, Gregory JFIII. (1999). Polymorphisms of methylenetetrahydrofolate reductase and other enzymes: Metabolic significance, risks and impact on folate requirement. Journal of Nutrition. 129: 919-922. Choay P. (2000). [Micronutritional requirements during women’s life.] Annales pharmaceutiques francaises. Dec, 58(6 Suppl): 443-7. Erickson JD, et al. (2002). Folate status in women of childbearing age, by race/ethnicity – United States, 1999-2000. MMWR. Sept 13: 808-810. Fodinger M, Mannhalter C, Wolfl G, Pabinger I, Muller E, Schmid R, Horl W, Sunder Plassmann G. (1997). Mutation (667 C to T) in the methylenetetrahydrofolate reductase gene aggravates hyperhomocysteinemia in hemodialysis patients. Kidney International. Aug; 52(2): 517-23. Herrmann W. (2001). The importance of hyperhomocysteinemia as a risk factor for diseases: An overview. Clinical Chemistry and Laboratory Medicine. Aug, 39(8): 666-74. Hustad S, Ueland P, Vollset S, Zhang Y, Bjorke Monsen A, Schneede J. (2000). Riboflavin as a determinant of plasma total homocysteine: Effect modification by the methylenetetrahydrofolate reductase C677T polymorphism. Clinical Chemistry. Aug 46(8 Pt 1): 1065-71. Jacques PF, Kalmbach R, Bagley PJ, Russo GT, Rogers G, Wilson PW, Rosenberg IH, Selhub. (2002). The relationship between riboflavin and plasma total homocysteine in the Framingham Offspring cohort is influenced by folate status and the C677T transition in the methylenetetrahydrofolate reductase gene. The Journal of Nutrition. Feb, 132(2): 283-8. James S, Pogribna M, Pogribny I, Melnyk S, Hine R, Gibson J, Yi P, Tafoya D, Swenson D, Wilson V, Gaylor D. (1999). Abnormal folate metabolism and mutation in the methylenetetrahydrofolate reductase gene may be maternal risk factors for Down syndrome. American Journal of Clinical Nutrition. Oct 70(4): 495-501. Koga T; Claycombe K, Meydani M. (2002). Homocysteine increases monocyte and T- cell adhesion to human aortic endothelial cells. Atherosclerosis. Apr, 161(2):365-74.