Mitochondrial Haplogroups A and M7a Confer a Genetic Risk for Coronary Atherosclerosis in the Japanese Elderly: An Autopsy Study of 1,536 Patients

作者：Sawabe Motoji^*; Tanaka Masashi; Chida Kouji; Arai Tomio; Nishigaki Yutaka; Fuku Noriyuki; Mieno Makiko Naka; Kuchiba Aya; Tanaka Noriko

来源：Journal of Atherosclerosis and Thrombosis, 2011, 18(2): 166-175.

• Atherosclerosis
• Coronary artery
• Myocardial infarction
• Mitochondrial genome
• Haplogroup

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.

• 出版日期2011