Recurrent coronary events are not increased in postinfarction patients with methylenetetrahydrofolate reductase gene C677T polymorphism

Hyperhomocysteinemia has been reported as a risk factor for coronary artery disease, premature myocardial infarction, stroke, and venous thrombosis.(1-5) One common cause for hyperhomocysteinemia is a genetic defect involving the thermolabile variant of methylenetetrahydrofolate reductase (MTHFR),(6,7) which is characterized by a point mutation at the nucleotide position 677 from cytosine to thymine (C677T) and amino acid substitution of alanine by valine. The MTHFR enzyme catalyzes the reduction of 5,10-methylenetetrahydrofolate to 5-methylenetetrahydrofolate, which is essential for remethylation of homocysteine to methionine.(6) Prior studies have shown that subjects with homozygosity (TT genotype) of the enzyme exhibit an increased incidence of coronary artery disease(6,8-10) and ischemic stroke.(11) However, contradictory studies(12-14) exist. In this present study, we utilized the large, prospective Thrombogenic Factors and Recurrent Coronary Events (THROMBO) study(15) with high-risk postinfarction patients to determine the association of the TT genotype in the MTHFR gene with various thrombogenic and lipid factors, as well as its association with the risk of recurrent coronary events (death, nonfatal myocardial infarction, or unstable angina).