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

• Sawabe Motoji

  Department of Pathology and Bioresource Center for Geriatric Research, Tokyo Metropolitan Geriatric Hospital.

• Tanaka Masashi

  Department of Genomics for Longevity and Health, Tokyo Metropolitan Institute of Gerontology.

• Chida Kouji

  Department of Pathology and Bioresource Center for Geriatric Research, Tokyo Metropolitan Geriatric Hospital.

• Arai Tomio

  Department of Pathology and Bioresource Center for Geriatric Research, Tokyo Metropolitan Geriatric Hospital.

• Nishigaki Yutaka

  Department of Genomics for Longevity and Health, Tokyo Metropolitan Institute of Gerontology.

• Fuku Noriyuki

  Department of Genomics for Longevity and Health, Tokyo Metropolitan Institute of Gerontology.

• Naka Mieno Makiko

  Department of Medical Informatics, Center for Information, Jichi Medical University, Shimotsuke.

• Kuchiba Aya

  Genetics Division, National Cancer Center Research Institute.

• Tanaka Noriko

  Department of Biostatistics, Harvard School of Public Health.

Bibliographic Information

Other Title

• Mitochondrial DNA analysis of Hokkaido Jomon skeletons: Remnants of archaic maternal lineages at the southwestern edge of former Beringia

Abstract

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.<BR>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.<BR>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).<BR>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.

Journal

• Journal of Atherosclerosis and Thrombosis

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

  Japan Atherosclerosis Society

Keywords

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

Details

• CRID: 1390282679409730048
• NII Article ID: 130004444492
• DOI: 10.5551/jat.6742
• DOI: 10.1002/ajpa.21561
• ISSN: 18803873
• ISSN: 10968644
• ISSN: 13403478
• ISSN: 00029483
• Web Site: https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fajpa.21561
• Web Site: https://onlinelibrary.wiley.com/doi/pdf/10.1002/ajpa.21561
• Web Site: https://search.jamas.or.jp/link/ui/2012030833
• Text Lang: en
• Data Source:
  • JaLC
  • Crossref
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed