Mitochondrial haplogroups A and M7a confer a genetic risk for coronary atherosclerosis in the japanese Elderly: An autopsy study of 1,536 patients

Aim: we previously reported significant associations between mitochondrial single nucleotide polymorphisms (mtsnps) and myocardial infarction,atherothrombotic cerebral infarction,metabolic syndrome and type 2 diabetes. here,we assessed the hypothesis that mtsnps may confer a risk for atherosclerosis,the most important intermediate phenotype of ischemic cardiovascular events. methods: the subjects were 1,536 consecutive autopsy cases (827 men and 709 women). the average age at death was 80 years. the severity of coronary atherosclerosis was semi-quantitatively examined on cut sections. we examined 149 mtsnps using the pcr-luminex method,with a success rate of 97%. phylogenetic tree analysis yielded 36 haplogroups. multiple logistic regression analysis was performed after adjustments for sex,age,and conventional cardiovascular risk factors. results: among the 45 mtsnps with minor genotype frequencies <0.05,6 mtsnps were associated with coronary atherosclerosis. among 10 haplogroups with frequencies <0.04,haplogroups a and m7a were significantly associated with coronary atherosclerosis,with odds ratios (95% confidence intervals) of 1.80 (1.09-2.97; p 0.023) and 1.92 (1.23-3.01; p = 0.004),respectively. haplogroup d4a,which was previously reported to be associated with extreme longevity in a japanese population,was associated with pathological myocardial infarction in men with an odds ratio of 2.05 (1.01-4.14; p = 0.046). conclusions: the mitochondrial haplogroups a and m7a confer a significant risk for coronary atherosclerosis in the japanese. the mitochondrial haplogroup may contribute some genetic risk for coronary heart disease.