Mitochondrial genome polymorphisms associated with performance in marathon and obesity

由于线粒体在胰腺β细胞的胰岛素分泌和骨骼肌的胰岛素抵抗中都起着关键作用，我们进行了一项大规模的关联研究，以确定线粒体单倍群对代谢综合征（MS）的抵抗或易感性。研究人群包括1337名无血缘关系的日本人，其中包括871名多发性硬化症患者和466名对照组。测定了线粒体基因组编码区25个多态性的基因型，并将其划分为10个主要单倍群。多因素logistic回归分析调整了年龄和吸烟的流行程度，结果显示单倍群N9a、Gl和D5与女性MS耐药性显著相关。我们还进行了一项大规模关联研究，以确定线粒体单倍群对2型糖尿病（T2DM）具有抵抗力或易感性。研究人群包括2906名无血缘关系的日本人，包括1289名2型糖尿病患者和1617名对照组。测定了线粒体基因组编码区25个多态性的基因型，并将其划分为10个主要单倍群。多因素logistic回归分析显示，单倍群F与T2DM易感性显著相关（P = 0.0028），优势比为1.54。相比之下，具有N9a单倍群的受试者患此病的风险较低（P = 0.0233），优势比为0.64。在女性中，单倍群N9a对2型糖尿病具有显著的保护作用（P = 0.0042），优势比为0.27。具有F和A单倍群的女性患2型糖尿病的风险增加（OR分别为1.78和1.67），而具有F单倍群的男性患2型糖尿病的风险增加（OR为1.43）。这些线粒体单核苷酸多态性的单倍群可能为预测多发性硬化症和2型糖尿病的遗传风险提供信息。少

Since mitochondria play pivotal roles both in insulin secretion from the pancreatic beta cells and in insulin resistance of skeletal muscles, we performed a large-scale association study to identify mitochondrial haplogroups that confer resistance against or susceptibility to metabolic syndrome (MS). The study population comprised 1337 unrelated Japanese individuals, including 871 subjects with MS and 466 controls. The genotypes for 25 polymorphisms in the coding region of the mitochondrial genome were determined, and the haplotypes were classified into 10 major haplogroups. Multivariate logistic regression analysis with adjustment for age and the prevalence of smoking revealed that the haplogroups N9a, Gl, and D5 were significantly associated with resistance against MS in women. We also performed a large-scale association study to identify mitochondrial haplogroups that confer resistance against or susceptibility to type 2 diabetes (T2DM). The study population comprised 2906 unrelated … More Japanese individuals, including 1289 patients with T2DM and 1617 controls. The genotypes for 25 polymorphisms in the coding region of the mitochondrial genome were determined, and the haplotypes were classified into 10 major haplogroups. Multivariate logistic regression analysis with adjustment for age and the prevalence of smoking revealed that the haplogroup F was significantly associated with susceptibility to T2DM (P = 0.0028) with an odds ratio of 1.54. In contrast, subjects with the haplogroup N9a tended to have a reduced risk for this condition (P = 0.0233), having an odds ratio of 0.64. In women, the haplogroup N9a was significantly protective against T2DM (P = 0.0042), showing an odds ratio of 0.27. Women with both haplogroups F and A tended to have an increased risk for T2DM (OR 1.78 and 1.67, respectively), whereas men with the haplogroup F tended to have an increased risk for it (OR 1.43). Haplogrouping for these mitochondrial single nucleotide polymorphisms may prove informative for predicting the genetic risk for MS and T2DM. Less