PMID- 10715806 OWN - NLM STAT- MEDLINE DCOM- 20000331 LR - 20191025 IS - 0954-6928 (Print) IS - 0954-6928 (Linking) VI - 11 IP - 1 DP - 2000 Feb TI - Genetic polymorphism of 5,10-methylenetetrahydrofolate increases risk of myocardial infarction and is correlated to elevated levels of homocysteine in the Japanese general population. PG - 47-51 AB - 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 (MTHFR) gene [alanine/valine (A/V) polymorphism], one of the key enzymes involved in catalyzing the remethylation of homocysteine, has recently been reported. OBJECTIVE: To evaluate the incidence of the MTHFR genotypes and their significance in determining the risk for myocardial infarction of Japanese men. METHOD: The subjects consisted of 199 healthy men (mean age, 60 years) and 230 male patients with myocardial infarction (mean age, 59 years). The coronary-artery lesions were evaluated by coronary angiography. The MTHFR genotype was analyzed by polymerase chain reaction and then by digestion with Hinfl. Total plasma levels of homocysteine for each MTHFR genotype were compared with those in healthy controls. RESULTS: The prevalences of the A and V alleles among the healthy male subjects were 0.652 and 0.348 in the Hardy-Weinberg equilibrium. The total levels of homocysteine in the plasma of the healthy male subjects were 8.6 +/- 3.3, 8.9 +/- 4.1, and 11.6 +/- 5.6 mumol/l, for AA, AV, and VV genotypes, respectively. Individuals with the VV homozygous mutant genotype thus had the highest plasma levels of homocysteine. Logistic analysis revealed that the levels 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 with myocardial infarction (mean age, 59 years) than it was among the control subjects (17.0 versus 10.6%, P < 0.05). However, there were no differences 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. FAU - Nakai, K AU - Nakai K AD - Second Department of Internal Medicine & Memorial Heart Center, Iwate Medical University, Tokyo, Japan. knakai@iwate-med.ac.jp FAU - Fusazaki, T AU - Fusazaki T FAU - Suzuki, T AU - Suzuki T FAU - Ohsawa, M AU - Ohsawa M FAU - Ogiu, N AU - Ogiu N FAU - Kamata, J AU - Kamata J FAU - Kawazoe, K AU - Kawazoe K FAU - Nakai, K AU - Nakai K FAU - Itoh, C AU - Itoh C FAU - Yanagisawa, M AU - Yanagisawa M FAU - Ishida, T AU - Ishida T FAU - Hiramori, K AU - Hiramori K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Coron Artery Dis JT - Coronary artery disease JID - 9011445 RN - 0 (Vitamins) RN - 0LVT1QZ0BA (Homocysteine) RN - EC 1.5.1.5 (Methylenetetrahydrofolate Dehydrogenase (NADP)) SB - IM MH - Cohort Studies MH - Homocysteine/adverse effects/*blood MH - Humans MH - Japan MH - Male MH - Methylenetetrahydrofolate Dehydrogenase (NADP)/*genetics MH - Middle Aged MH - Myocardial Infarction/blood/*genetics/prevention & control MH - Polymerase Chain Reaction MH - Risk Factors MH - Vitamins/therapeutic use EDAT- 2000/03/15 00:00 MHDA- 2000/03/15 00:01 CRDT- 2000/03/15 00:00 PHST- 2000/03/15 00:00 [pubmed] PHST- 2000/03/15 00:01 [medline] PHST- 2000/03/15 00:00 [entrez] AID - 10.1097/00019501-200002000-00009 [doi] PST - ppublish SO - Coron Artery Dis. 2000 Feb;11(1):47-51. doi: 10.1097/00019501-200002000-00009.