Lawrence Appel

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

S H Jee; T H Beaty; I Suh; Y Yoon; L J Appel (Profiled Authors: Lawrence Appel; Terri Beaty)

Department of Epidemiology and Disease Control, Yonsei University Graduate School of Health Science and Management, CPO POB 8044, Seoul, South Korea. jsunha@yumc.yonsei.ac.kr
Atherosclerosis 2000;153(1):161-8.

The methylenetetrahydrofolate reductase (MTHFR) gene has been associated with increased risk for cardiovascular disease in some, but not all studies. Our data sources included a MEDLINE search of the literature published before December 1998, a bibliography review, and expert consultation. Of 23 studies initially identified, 18 (9855 persons) met the inclusion criteria. Information on sample size, study design, Hardy-Weinberg equilibrium, method of genotype determination, plasma folate and homocysteine were abstracted by two reviewers using a standardized protocol. The overall odds ratio of the MTHFR gene on cardiovascular disease was estimated using the Mantel-Haenzel method. From 12 studies with angiographically-confirmed coronary artery disease (CAD), the overall odds ratio (OR) for CAD among those with heterozygous (V/A) was 1.3 (95% CI, 1.1-1.5), while it was 1.4 (1.2-1.6) for the homozygous mutant (V/V) compared to those with homozygous normal (A/A). However, the overall odds ratio for CAD among those with the V/V genotype versus 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 infarction (MI), the overall OR of MI was 1.0 (0.8-1.1) for those with the V/A genotype and 0.9 (0.7-1.1) for those with the V/V genotype, respectively; none of these ORs for MI was statistically significant. The MTHFR gene is associated with increased risk for CAD in Japan, but not in other populations.

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