Mitochondrial haplogroups A and M7a confer a genetic risk for coronary atherosclerosis in the Japanese elderly: an autopsy study of 1,536 patients

J Atheroscler Thromb. 2011;18(2):166-75. doi: 10.5551/jat.6742. Epub 2010 Nov 19.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Asian Continental Ancestry Group / genetics*
  • Autopsy
  • Base Sequence
  • Coronary Artery Disease / etiology*
  • Coronary Artery Disease / genetics*
  • Coronary Artery Disease / pathology
  • DNA, Mitochondrial / genetics*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Haplotypes
  • Humans
  • Japan
  • Logistic Models
  • Longevity / genetics
  • Male
  • Myocardial Infarction / etiology
  • Myocardial Infarction / genetics
  • Myocardial Infarction / pathology
  • Nucleic Acid Conformation
  • Phylogeny
  • Polymorphism, Single Nucleotide*
  • RNA, Ribosomal / chemistry
  • RNA, Ribosomal / genetics
  • Risk Factors


  • DNA, Mitochondrial
  • RNA, Ribosomal
  • RNA, ribosomal, 12S