Distribution in healthy and coronary populations of the methylenetetrahydrofolate reductase (MTHFR) C677T mutation.

Modest elevations of circulating homocyst(e)ine are common in patients with vascular disease. We explored in normal and coronary artery disease (CAD) populations the distribution of a mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene that results in enzyme thermolability and reduced activity and in homocyst(e)ine elevation to assess its relevance to risk. We identified the C to T substitution at the MTHFR locus and compared the distributions of genotypes in 565 patients aged < or = 65 years without and with angiographically documented CAD and in 225 healthy subjects. In the patients, we also assessed interrelations between genotypes and CAD occurrence and severity, as well as standard risk factors. The frequency of homozygotes for the mutation was the same in patients with and without CAD and in healthy subjects (11.6%, 11.0%, and 10.7%, respectively: P > .5 for each). There was also no excess among the 419 patients with severe disease (ie, one or more vessels with > 50% luminal obstruction) compared with those with no or mild CAD (odds ratio: 1.004; 95% confidence interval: 0.59 to 1.70). Homozygosity for the mutation was also not associated with a history of myocardial infarction or the presence or severity of angina. However, body mass index increased linearly with the presence of the mutant allele (P = .005), and the mutation and hypertension were weakly associated (P = .036). We conclude that the MTHFR genotype is not a risk factor for coronary disease in this Australian population but that the strong association found with body mass index should be explored further.