Journal Article

Age Dependence of the Influence of Methylenetetrahydrofolate Reductase Genotype on Plasma Homocysteine Level

Loretta D. Spotila, Paul F. Jacques, Peter B. Berger, Karla V. Ballman, R. Curtis Ellison and Rima Rozen

in American Journal of Epidemiology

Published on behalf of Johns Hopkins Bloomberg School of Public Health

Volume 158, issue 9, pages 871-877
Published in print November 2003 | ISSN: 0002-9262
Published online November 2003 | e-ISSN: 1476-6256 | DOI:
Age Dependence of the Influence of Methylenetetrahydrofolate Reductase Genotype on Plasma Homocysteine Level

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An elevated plasma homocysteine level is a risk factor for cardiovascular disease and is often observed in other common disorders, including neural tube defects, pregnancy complications, and Alzheimer’s disease. Plasma homocysteine level is affected by vitamin intake and by sequence variation in enzymes of homocysteine metabolism. One such enzyme, methylenetetrahydrofolate reductase (MTHFR), synthesizes 5-methyltetrahydrofolate, utilized in homocysteine remethylation to methionine. A variant of the MTHFR gene at base pair 677 is associated with reduced activity, increased thermolability, and hyperhomocysteinemia. This variant has been reported to increase risk of the aforementioned disorders. However, not all studies examining disease risk with respect to MTHFR genotype have reported a statistically significant relation. The current authors hypothesized that the effect of the variant might be stronger in younger age groups, as is the case with other genetic risk factors. Thus, the authors examined data from three North American studies: a study of mothers of spina bifida children and control mothers (1995–1996; n = 136); the National Heart, Lung, and Blood Institute Family Heart Study (1994–1995; n = 537); and a Mayo Clinic study of patients undergoing coronary angiography (1998–1999; n = 504). In each study, the effect of MTHFR genotype on plasma homocysteine level was statistically significant only in younger age groups. Failure to examine younger patients separately may explain why some studies have found no association between the genotype and cardiovascular disease.

Keywords: amine oxidoreductases; cardiovascular diseases; folic acid; genotype; homocysteine; neural tube defects; vitamins; Abbreviations: FHS, Family Heart Study; MCS, Mayo Clinic study; MTHFR, methylenetetrahydrofolate reductase; SBS, spina bifida study.

Journal Article.  4776 words. 

Subjects: Public Health and Epidemiology

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