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 dise ase (CAD) populations the distribution of a mutation in the 5,10-methy lenetetrahydrofolate reductase (MTHFR) gene that results in enzyme the rmolability and reduced activity and in homocyst(e)ine elevation to as sess its relevance to risk. We identified the C to T substitution at t he MTHFR locus and compared the distributions of genotypes in 565 pati ents aged less than or equal to 65 years without and with angiographic ally documented CAD and in 225 healthy subjects. In the patients, we a lso assessed interrelations between genotypes and CAD occurrence and s everity, as well as standard risk factors. The frequency of homozygote s for the mutation was the same in patients with and without CAD and i n healthy subjects (11.6%, 11.0%, and 10.7%, respectively; P>.5 for ea ch). There was also no excess among the 419 patients with severe disea se tie, one or more vessels with >50% luminal obstruction) compared wi th those with no or mild CAD (odds ratio: 1.004: 95% confidence interv al: 0.59 to 1.70). Homozygosity for the mutation was also not associat ed with a history of myocardial infarction or the presence or severity of angina. However, body mass index increased linearly with the prese nce of the mutant allele (P=.005), and the mutation and hypertension w ere 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 e xplored further.