title: The methylenetetrahydrofolate reductase gene is associated with increased cardiovascular risk in Japan, but not in other populations.
abstract: 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.
authors.affiliation: 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
authors.forename: S H
authors.initials: SH
authors.lastname: Jee
authors.forename: T H
authors.initials: TH
authors.lastname: Beaty
authors.forename: I
authors.initials: I
authors.lastname: Suh
authors.forename: Y
authors.initials: Y
authors.lastname: Yoon
authors.forename: L J
authors.initials: LJ
authors.lastname: Appel
mesh_terms: D044466:Asian People / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000235:genetics*; D003327:Coronary Disease / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007564:Japan; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D009203:Myocardial Infarction / Q000235:genetics; D016017:Odds Ratio; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*
chemical_list: D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)