title: Correlation of a common mutation in the methylenetetrahydrofolate reductase gene with plasma homocysteine in patients with premature coronary artery disease.
abstract: Mild hyperhomocysteinemia, a risk factor for occlusive arterial disease, can be caused by disruptions of homocysteine metabolism. Methylenetetrahydrofolate reductase (MTHFR) catalyzes the synthesis of 5-methyltetrahydrofolate, the methyl donor for homocysteine remethylation to methionine. A common mutation in MTHFR, an alanine-to-valine substitution, may contribute to mild hyperhomocysteinemia in coronary artery disease (CAD). To test this hypothesis, we studied 152 patients with CAD by mutation analysis, MTHFR enzymatic assays, and measurements of plasma homocysteine and several vitamins. The MTHFR mutation was associated with reduced enzymatic activity and increased enzyme thermo-lability in these patients. The difference in the prevalence of the homozygous mutant genotype between the CAD patients (14%) and an unmatched group of healthy subjects (10%) was not significant. However, individuals with the homozygous mutant genotype had higher plasma homocysteine, particularly when plasma folate was below the median value. This genetic-environmental interaction is proposed to be a risk factor for CAD.
authors.affiliation: Department of Human Genetics, McGill University, Montreal, Canada.
authors.forename: B
authors.initials: B
authors.lastname: Christensen
authors.forename: P
authors.initials: P
authors.lastname: Frosst
authors.forename: S
authors.initials: S
authors.lastname: Lussier-Cacan
authors.forename: J
authors.initials: J
authors.lastname: Selhub
authors.forename: P
authors.initials: P
authors.lastname: Goyette
authors.forename: D S
authors.initials: DS
authors.lastname: Rosenblatt
authors.forename: J
authors.initials: J
authors.lastname: Genest
authors.forename: R
authors.initials: R
authors.lastname: Rozen
mesh_terms: D000328:Adult; D003327:Coronary Disease / Q000097:blood / Q000235:genetics*; D005260:Female; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D009154:Mutation; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*
chemical_list: D006710:Homocysteine; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)