The methylenetetrahydrofolate reductase gene is associated with increased cardiovascular risk in Japan, but not in other populations

The methylenetetrahydrofolate reductase (MTHFR) gene has been associated wi th increased risk for cardiovascular disease in some, but not all studies. Our data sources included a MEDLINE search of the literature published befo re December 1998, a bibliography review, and expert consultation. Of 23 stu dies initially identified, 18 (9855 persons) met the inclusion criteria. In formation on sample size, study design, Hardy-Weinberg equilibrium, method of genotype determination, plasma folate and homocysteine were abstracted b y two reviewers using a standardized protocol. The overall odds ratio of th e MTHFR gene on cardiovascular disease was estimated using the Mantel-Haenz el method. From 12 studies with angiographically-confirmed coronary artery disease (CAD), the overall odds ratio (OR) for CAD among those with heteroz ygous (V/A) was 1.3 (95% CI, 1.1-1.5), while it was 1.4 (1.2-1.6) for the h omozygous mutant (V/V) compared to those with homozygous normal (A/A). Howe ver, the overall odds ratio for CAD among those with the V/V genotype versu s A/A genotype was not statistically significant (OR: 1.1; 95% CI: 0.9-1.3) after excluding three Japanese studies. The corresponding OR for the three Japanese studies was 2.0 (1.6-2.7). For six studies with myocardial infarc tion (MI), the overall OR of MI was 1.0 (0.8-1.1) for those with the V/A ge notype and 0.9 (0.7-1.1) for those with the V/V genotype, respectively; non e of these ORs for MI was statistically significant. The MTHFR gene is asso ciated with increased risk for CAD in Japan, but not in other populations. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.