Plasma hyperhomocysteinemia, MTHFR polymorphism and thromboembolic disease: an example of gene-nutrition interactions in chronic disease.

Many studies have shown that hyperhomocysteinemia may be an independent risk factor for thromboembolic disease. However, the results among studies and populations have not been consistent. Furthermore, the possible mechanisms of hyperhomocysteinemia in vascular diseases are controversial. Mutations in the MTHFR (5,10-methylenetetrahydrofolate reductase) gene, resulting in rising levels of plasma homocysteine or dietary folate, and vitamin B6 and B12 intake deficiency, may play a role in this complicated process. In this editorial comment, I discuss the metabolism of homocysteine, hyperhomocysteinemia in vascular diseases, and MTHFR deficiency (MTHFR gene mutation) and/or nutritional deficiency and their impact on thromboembolic diseases. Finally, based on previous study results, the possible gene-nutrient interactions in the pathophysiology of hyperhomocysteinemia in thromboembolic diseases are clarified. Homocysteine, a sulfur-containing amino acid, is an intermediate product in methionine metabolism. Most of the dietary methionine is converted to S-adenosylmethionine and then to S-adenosylhomocysteine. Hydrolysis of S-adenosylhomocysteine leads to adenosine and homocysteine. Homocysteine may then be metabolized either by transsulfuration or transmethylation, depending on the availability of methionine. Several factors are associated with the regulation of methionine and homocysteine metabolism that depends on the presence of adequate enzyme levels and their kinetic properties. In general, plasma homocysteine levels Plasma Hyperhomocysteinemia, MTHFR Polymorphism and Thromboembolic Disease: An Example of Gene-nutrition Interactions in Chronic Disease