Methylenetetrahydrofolate reductase 677 C/T genotype and cardiovascular disease mortality in postmenopausal women

Methylenetetrahydrofolate reductase (MTHFR) is involved in the reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. A 677 C/T sing le nucleotide polymorphism localized in the MTHFR gene is associated with b oth thermolability and reduced activity of the enzyme and is associated wit h increased homocysteine levels. The authors investigated the relation betw een the MTHFR 677 C/T polymorphism and risk of cardiovascular disease morta lity in a cohort study of 12,239 women initially aged 52-67 years with a ma ximum follow-up time of 18 years (1976-1995; 153,732 woman-years of follow- up). The cardiovascular disease mortality rate was highest among women with the MTHFR 677 CC wild-type genotype and lowest among MTHFR 677 TT homozygo tes, In comparison with women with the 677 CC wild-type genotype, age-adjus ted rate ratios were 0.7 (95% confidence interval: 0.5, 0.9) for 677 CT het erozygotes and 0.6 (95% confidence interval: 0.4, 1.0) for 677 TT homozygot es. The possibility that this relation is a chance finding must be consider ed, because the relation is weak and of borderline significance. However, i t provides an important argument against the view that increased levels of homocysteine directly raise cardiovascular disease risk.