Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:569-573
© 1997 American Heart Association, Inc.
Articles |
Correlation of a Common Mutation in the Methylenetetrahydrofolate Reductase Gene With Plasma Homocysteine in Patients With Premature Coronary Artery Disease
From the Departments of Human Genetics, Pediatrics, and Biology (B.C., P.F., P.G., D.S.R., R.R.) and Department of Medicine (B.C., D.S.R.), McGill University, Montreal, Canada; Institut de Recherches Cliniques de Montréal (S.L.-C., J.G.), Canada; USDA Human Nutrition Research Center on Aging at Tufts University (J.S.), Boston, Mass; Hôtel-Dieu Hospital (J.G.), Montreal, Canada.
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 thermolability 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.
Key Words: homocysteine • methylenetetrahydrofolate reductase • folic acid • genes • mutation
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