Genetic polymorph ism of 5,10-methylenetetrahydrofolate increases risk of myocardial infarction and is correlated to elevated levels of homocysteine in the Japanese general population

Background Hyperhomocysteinemia, an independent and graded risk factor for coronary artery disease, can result from both environmental and hereditary factors. C677T mutation of the 5,10-methylenetetrahydrofolate reductase (MT HFR) gene [alanine/valine (A/V) polymorphism], one of the key enzymes invol ved in catalyzing the remethylation of homocysteine, has recently been repo rted. Objective To evaluate the incidence of the MTHFR genotypes and their signif icance in determining the risk for myocardial infarction of Japanese men. Method The subjects consisted of 199 healthy men (mean age, 60 years) and 2 30 male patients with myocardial infarction (mean age, 59 years). The coron ary-artery lesions were evaluated by coronary angiography. The MTHFR genoty pe was analyzed by polymerase chain reaction and then by digestion with Hin fI. Total plasma levels of homocysteine for each MTHFR genotype were compar ed with those in healthy controls. Results The prevalences of the A and V alleles among the healthy male subje cts were 0.652 and 0.348 in the Hardy-Weinberg equilibrium. The total level s of homocysteine in the plasma of the healthy male subjects were 8.6+/-3.3 , 8.9+/-4.1, and 11.6+/-5.6 mu mol/l, for AA, AV, and VV genotypes, respect ively Individuals with the VV homozygous mutant genotype thus had the highe st plasma levels of homocysteine, Logistic analysis revealed that the level s of high-density lipoprotein cholesterol, hypertension, diabetes mellitus, MTHFR VV genotype, and triglycerides were all independent risk factors for myocardial infarction. The VV genotype was more prevalent among patients w ith myocardial infarction (mean age, 59 years) than it was among the contro l subjects (17.0 versus 10.6%, P < 0.05). However, there were no difference s in the numbers of stenotic coronary arteries among the MTHFR genotypes. Conclusion The VV genotype of MTHFR increases plasma levels of homocysteine in healthy controls, and this mutation indicates a genetic predisposition toward a greater than normal risk of myocardial infarction for Japanese men . Coronary Artery Dis 11:47-51 (C) 2000 Lippincott Williams & Wilkins.