Abstract
Superoxide, which mitochondria mainly produce in vascular endothelial cells, plays an important role in the pathogenesis of atherosclerosis and coronary artery disease. Accordingly, mitochondrial functional differences are thought to be one of the most important factors for the risk of myocardial infarction among various individuals. In the present study, we surveyed mitochondrial haplogroups associated with myocardial infarction in Japanese subjects. The study population comprised 2,137 unrelated Japanese individuals, including 1,181 subjects with a first myocardial infarction (920 males, 261 females) and the control subjects (522 males, 434 females). Twenty-eight mitochondrial single nucleotide polymorphisms of 12 major mitochondrial haplogroups (A, B, D4, D5, F, G1, G2, M7a, M7b, M7c, N9a, and N9b) were determined by use of 28-plex PCR and fluorescent beads combined with sequence-specific oligonucleotide probes. After adjustment for age, sex, body mass index, and prevalence of smoking, hypertension, hypercholesterolemia, and type 2 diabetes, a significantly (P = 0.0019) lower prevalence of haplogroup N9b was detected in subjects with myocardial infarction than in the controls. Especially, the prevalence of this haplogroup was significantly lower (P = 0.0007) in the male subjects with the disease than in the male controls. In contrast, there were trends towards higher prevalence of the disease in haplogroup G1 for males (P < 0.05). No significant haplogroup-related associations were detected for females. Our data suggest that haplogroup N9b confers resistance against myocardial infarction in Japanese males.
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Acknowledgments
This work was supported in part by a grants-in-aid [A (2)-15200051 to M.T.] from the Ministry of Education, Culture, Sports, Science and Technology by a grant from the Third-Term Comprehensive 10-year Strategy for Cancer Control (to M.T.), by grant 17A-10 from the program Research Grants for Nervous and Mental Disorders of the Ministry of Health, Labour, and Welfare (to M.T.), and by grants for scientific research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (no. 15209021 to Y.Y.) and the Gifu Prefectural Science and Technology Promotion Center (to Y.Y.).
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In addition to the authors, the following individuals participated in the study: Y. Matsuno and M. Tomita (Gifu Prefectural Gifu Hospital, Gifu); M. Oguri, K. Yajima, T. Hibino, and T. Kameyama (Gifu Prefectural Tajimi Hospital, Tajimi); S. Tanihata (Gifu Prefectural Gero Hotspring Hospital, Gero); and nursing and laboratory staff of the participating hospitals. We also thank Dr. Masafumi Ito (Gifu International Institute of Biotechnology) for financial support.
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Nishigaki, Y., Yamada, Y., Fuku, N. et al. Mitochondrial haplogroup N9b is protective against myocardial infarction in Japanese males. Hum Genet 120, 827–836 (2007). https://doi.org/10.1007/s00439-006-0269-z
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DOI: https://doi.org/10.1007/s00439-006-0269-z