Mitochondrial genome polymorphisms associated with performance in marathon and obesity

线粒体基因组多态性与马拉松和肥胖表现相关

• 批准号: 15200051
• 负责人: TANAKA Masashi
• 金额: $ 13.89万
• 依托单位: Tokyo Metropolitan Institute of Gerontology (2004-2005)Gifu International Institute of Biotechnology (2003)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15200051/
• 关键词: mitochondrial genome; obesity; type 2 diabetes; metabolic syndrome; haplogroup; myocardial infarction; Parkinson disease; lifestyle-related diseases; ミトコンドリアゲノム多型; マラソン; ミトコンドリア電子伝達系; ATP合成酵素; 一塩基多型; ミトコンドリアDNA多型; NADH脱水素酵素; アルツハイマー病

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

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起关键作用，我们进行了大规模的关联研究，以确定线粒体单倍型群，赋予抵抗或易感性代谢综合征（MS）。研究人群包括1337名无关的日本人，包括871名MS受试者和466名对照者。对线粒体基因组编码区的25个多态性位点进行了基因型分析，并将其分为10个主要单倍型群。校正年龄和吸烟率的多变量logistic回归分析显示，单倍型群N9a、G1和D5与女性对MS的抵抗力显著相关。我们还进行了一项大规模的关联研究，以确定线粒体单倍型群，赋予抵抗或易感性2型糖尿病（T2DM）。研究人群包括2906名无关 ...更多信息 日本个体，包括1289例T2DM患者和1617例对照。对线粒体基因组编码区的25个多态性位点进行了基因型分析，并将其分为10个主要单倍型群。校正年龄和吸烟率后的多变量logistic回归分析显示，单倍群F与T2DM易感性显著相关（P = 0.0028），比值比为1.54。相比之下，具有单倍型群N9a的受试者倾向于具有这种情况的降低的风险（P = 0.0233），具有0.64的优势比。在女性中，单倍群N9a对T2DM具有显著的保护作用（P = 0.0042），比值比为0.27。具有单倍群F和A的女性倾向于增加T2DM的风险（OR分别为1.78和1.67），而具有单倍群F的男性倾向于增加其风险（OR 1.43）。这些线粒体单核苷酸多态性的单倍型分组可能被证明为预测MS和T2DM的遗传风险提供信息。少

项目成果

Identification of mitochondrial DNA polymorphisms that alter mitochondrial matrix pH and intracellular calcium dynamics.

线粒体DNA多态性的鉴定会改变线粒体基质pH和细胞内钙动力学。

• DOI: 10.1371/journal.pgen.0020128
• 发表时间: 2006-08
• 期刊: PLOS GENETICS
• 影响因子: 4.5
• 作者: Kazuno, An-a;Munakata, Kae;Nagai, Takeharu;Shimozono, Satoshi;Tanaka, Masashi;Yoneda, Makoto;Kato, Nobumasa;Miyawaki, Atsushi;Kato, Tadafumi
• 通讯作者: Kato, Tadafumi

Yamada Y, Tanaka M, Nozawa, Y et al.: "Association of a polymorphism of the phospholipase D(2) gene with the prevalence of colorectal cancer"J Mol Med. 81. 126-131 (2003)

Yamada Y，Tanaka M，Nozawa，Y 等人：“磷脂酶 D(2) 基因的多态性与结直肠癌患病率的关联”J Mol Med。

Iwao, N, Iwao S, Kobayashi F, Kazuo T, Tanaka M, et al.: "No association of the mitochondrial genotype (Mt5178A/C) with six cancers in Japanese population"Asian Pacific J Cancer Prev. 4. 331-336 (2003)

Iwao, N, Iwao S, Kobayashi F, Kazuo T, Tanaka M, et al.：“线粒体基因型 (Mt5178A/C) 与日本人群中的六种癌症没有关联”Asia Pacific J Cancer Prev。

Oxidative stress in mitochondria - Decision to survival and death of neurons in neurodegenerative disorders

• DOI: 10.1385/mn:31:1-3:081
• 发表时间: 2005-01-01
• 期刊: MOLECULAR NEUROBIOLOGY
• 影响因子: 5.1
• 作者: Naoi, M;Maruyama, W;Tanaka, M
• 通讯作者: Tanaka, M

Mitochondrial DNA sequence analysis of patients with 'atypical psychosis'

• DOI: 10.1111/j.1440-1819.2005.01404.x
• 发表时间: 2005-08-01
• 期刊: PSYCHIATRY AND CLINICAL NEUROSCIENCES
• 影响因子: 11.9
• 作者: Kazuno, AA;Munakata, K;Kato, T
• 通讯作者: Kato, T