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.
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.
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).
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.