Mitochondrial Haplogroups A and M7a Confer a Genetic Risk for Coronary Atherosclerosis in the Japanese Elderly: An Autopsy Study of 1,536 Patients
Mitochondrial Haplogroups A and M7a Confer a Genetic Risk for Coronary Atherosclerosis in the Japanese Elderly: An Autopsy Study of 1,536 Patients
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DOI：
10.5551/jat.6742
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发表时间：
2011-01-01
影响因子：
4.4
通讯作者：
Tanaka, Noriko
中科院分区：
文献类型：
--
作者：
Sawabe, Motoji;Tanaka, Masashi;Tanaka, Noriko
目的：我们之前报道过线粒体单核苷酸多态性（mtSNP）与心肌梗死、动脉粥样硬化性血栓性脑梗死、代谢综合征和2型糖尿病之间存在显着相关性。在这里，我们评估的假设，mtSNPs可能赋予动脉粥样硬化的风险，最重要的中间表型缺血性心血管events.Methods：受试者是1,536例连续尸检病例（827名男性和709名女性）。平均死亡年龄为80岁。冠状动脉粥样硬化的严重程度进行了半定量检查切片。我们使用PCR-Luminex方法检测了149个mtSNPs，成功率为97%。系统发育树分析得到36个单倍群。结果：在45个次要基因型频率> 0.05的mtSNPs中，有6个与冠状动脉粥样硬化相关。在频率> 0.04的10个单倍型群中，单倍型群A和M7 a与冠状动脉粥样硬化显著相关，比值比（95%置信区间）分别为1.80（1.09-2.97; p = 0.023）和1.92（1.23-3.01; p = 0.004）。单倍型D4 a，这是以前报道的与极端长寿的日本人口，与病理性心肌梗死的男性的优势比为2.05（1.01-4.14; p = 0.046）。结论：线粒体单倍型A和M7 a赋予冠状动脉粥样硬化在日本的显着风险。线粒体单倍型群可能对冠心病有一定的遗传风险。
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.