Increased homocysteine levels are an independent risk factor for coronary artery disease (CAD). A common genetic mutation (nucleotide 677 C-to-T) in methylenetetrahydrofolate reductase (MTHFR), an enzyme required for efficient homocysteine metabolism, creates a thermolabile enzyme with reduced activity. Homozygotes of MTHFR mutation represent 5% to 12% of general population in Canada, America, and Japan. In this study, we examined the distribution of the MTHFR genotypes in CAD patients and healthy volunteers and the association between the genotypes and the total homocysteine level (tHcy).

We screened 60 Korean patients with CAD (CAD group) and 97 healthy volunteers (control group) for the MTHFR 677 C-to-T mutation. Fasting and post-methionine-load tHcy level, folic acid, and vitamine B12 level were determined with other clinical variables in CAD group.

The frequency of the MTHFR V/V homozygous genotype was 20% in CAD group (with 40% heterozygous and 40% wild type) and 14% in control group (with 48% heterozygous and 38% wild type). In CAD group, homozygotes of MTHFR mutation had significant higher fasting tHcy level than wild type (homozygote, 18.83±6.37 micromol/L: wild type, 12.36±3.21 micromol/L: p<0.01). The tHcy level correlated with the age (r=0.425, p<0.01), the folate level (r=-0.534, p<0.01), and the presence of the mutant MTHFR gene (r=0.565, p<0.01) after adjustment of other clinical variables.

We find that homozygotes of MTHFR mutation have higher homocysteine level independent of folic acid in patients with CAD. Large case-control study needed to confirm whether MTHFR mutation increases the risk of CAD independent of plasma tHcy level.