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 single nucleotide polymorphism localized in the MTHFR gene is associated with both thermolability and reduced activity of the enzyme and is associated with increased homocysteine levels. The authors investigated the relation between the MTHFR 677 C/T polymorphism and risk of cardiovascular disease mortality in a cohort study of 12,239 women initially aged 52--67 years with a maximum 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 homozygotes. In comparison with women with the 677 CC wild-type genotype, age-adjusted rate ratios were 0.7 (95% confidence interval: 0.5, 0.9) for 677 CT heterozygotes and 0.6 (95% confidence interval: 0.4, 1.0) for 677 TT homozygotes. The possibility that this relation is a chance finding must be considered, because the relation is weak and of borderline significance. However, it provides an important argument against the view that increased levels of homocysteine directly raise cardiovascular disease risk.
Julius Center for Patient Oriented Research, Utrecht University Medical School, Utrecht, The Netherlands. m.roest@jc.azu.nl
M
M
Roest
Y T
YT
van der Schouw
D E
DE
Grobbee
M J
MJ
Tempelman
P G
PG
de Groot
J J
JJ
Sixma
J D
JD
Banga
D017677:Age Distribution; D000368:Aged; D001483:Base Sequence; D002318:Cardiovascular Diseases / Q000235:genetics* / Q000401:mortality*; D016022:Case-Control Studies; D002423:Cause of Death; D015331:Cohort Studies; D016001:Confidence Intervals; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D005838:Genotype; D006801:Humans; D008403:Mass Screening; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D008969:Molecular Sequence Data; D009426:Netherlands / Q000453:epidemiology; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D017698:Postmenopause; D011336:Probability; D012016:Reference Values; D012307:Risk Factors; D012680:Sensitivity and Specificity
D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)