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Genetic polymorphism of methylenetetrahydrofolate reductase and myocardial infarction. A case-control study
C Schmitz1, K Lindpaintner, P Verhoef
1Division of Cardiovascular Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA.
Insights
The C677T gene mutation, linked to higher homocysteine (tHcy) levels, does not increase myocardial infarction (MI) risk in this population. Folate intake did not alter this finding, suggesting the mutation isn't a reliable cardiovascular risk marker.
Area of Science:
- Genetics and Cardiovascular Health
- Biochemistry and Disease Risk
Background:
- Elevated total plasma homocysteine (tHcy) is a known risk factor for cardiovascular diseases.
- A common gene mutation (C677T) in methylenetetrahydrofolate reductase can lead to less active enzymes and higher tHcy levels.
- This mutation has been preliminarily linked to increased cardiovascular disease risk.
Purpose of the Study:
- To investigate the association between the C677T methylenetetrahydrofolate reductase gene mutation and myocardial infarction (MI) risk.
- To examine plasma total homocysteine (tHcy) levels in relation to the mutation.
- To determine if dietary folate intake modifies the mutation's effect on MI risk.
Main Methods:
- Case-control study involving 190 MI cases and 188 controls from the Boston Area Health Study.
- Genotyping for the C677T methylenetetrahydrofolate reductase mutation.
- Analysis of plasma tHcy levels and dietary folate intake (stratified by median intake).
Main Results:
- Genotype frequencies for the C677T mutation varied between cases and controls, but homozygosity (+/+ genotype) showed no significant increase in MI risk (Relative Risk=1.1, 95% CI 0.6-1.9).
- Plasma tHcy levels did not significantly differ across genotypes (-/-, +/-, +/+).
- Stratification by folate intake did not alter the observed risk or tHcy levels associated with the mutation.
Conclusions:
- Homozygosity for the C677T mutation is not associated with increased myocardial infarction risk in this US population.
- Dietary folate intake does not appear to modify the relationship between the C677T mutation and MI risk.
- The C677T mutation may not be a useful biomarker for cardiovascular risk in similar populations.
Background:
Elevated total plasma homocyst(e)ine (tHcy; the composite of homocysteine-derived moieties in their oxidized and reduced forms) levels are a risk factor for coronary heart disease, stroke, and venous thrombosis. tHcy plasma levels are influenced by folate, vitamins B6 and B12, as well as by hereditary factors. A point mutation (C677T) in the gene encoding methylenetetrahydrofolate reductase, an enzyme involved in homocysteine remethylation, has been reported to render the enzyme thermolabile and less active and has been associated with elevated tHcy in homozygous carriers (+/+ genotype) as well as with increased risk of premature cardiovascular disease.
Methods And Results:
We investigated whether this mutation influences risk for myocardial infarction (MI) and plasma levels of tHcy and whether this effect may be modified by dietary folate intake in 190 MI cases and 188 control subjects from the Boston Area Health Study. Genotype frequencies were 37.8% for -/-, 47.8% for +/-, and 14.4% for +/+ in the control group and 50.0% for -/-, 34.7% for +/-, and 15.3% for +/+ in the case group. The relative risk for MI associated with the +/+ genotype (compared with +/- and -/-) was 1.1 (95% CI, 0.6 to 1.9; P = .8). Stratification by folate intake values above and below the median did not significantly alter these results. Plasma tHcy levels were 9.9 +/- 2.7 mumol/L in -/- individuals, 10.6 +/- 3.8 mumol/L in +/- individuals, and 9.1 +/- 2.3 mumol/L in +/+ individuals (Ptrend = NS; determined in 68 cases and 59 control subjects).
Conclusions:
Our data show that homozygosity for the C677T mutation in this largely white, middle-class US population is not associated with increased risk for MI, irrespective of folate intake. This suggests that this mutation does not represent a useful marker for increased cardiovascular risk in this and in similar populations.