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发挥着关键作用，因此我们进行了一项大规模关联研究，以确定赋予研究人群抵抗或易感代谢综合征 (MS) 的线粒体单倍群。由 1337 名无关的日本个体组成，其中包括 871 名 MS 受试者和 466 名对照者，确定了线粒体基因组编码区 25 种多态性的基因型。单倍型被分为 10 个主要单倍群，并根据年龄和吸烟率进行调整，结果显示单倍群 N9a、G1 和 D5 与女性对 MS 的抵抗力显着相关。以确定对 2 型糖尿病 (T2DM) 具有抵抗力或易感性的线粒体单倍群。研究人群包括 2906 名无关的日本人，其中包括 1289 名患有 2 型糖尿病的患者。确定了 T2DM 和 1617 名对照者线粒体基因组编码区 25 个多态性的基因型，并将单倍型分为 10 个主要单倍群，并根据年龄和吸烟率进行了多元逻辑回归分析，结果显示单倍群 F 为与 T2DM 易感性显着相关（P = 0.0028），优势比为 1.54，相比之下，单倍群受试者。 N9a 患这种疾病的风险较低（P = 0.0233），在女性中，单倍群 N9a 对 T2DM 具有显着的保护作用（P = 0.0042），显示患有这两种疾病的女性的优势比为 0.27。单倍群 F 和 A 往往具有较高的 T2DM 风险（OR 分别为 1.78 和 1.67），而具有单倍群 F 的风险往往增加（OR 1.43），这些线粒体单核苷酸多态性的单倍群可能有助于预测 MS 和 T2DM 的遗传风险。

项目成果

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

• 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。

Crystallization of X-ray analysis of the N-terminal core domain of a tumor-associated human DEAD-box helicase, rck/p54

肿瘤相关人 DEAD-box 解旋酶 rck/p54 N 端核心结构域的 X 射线分析结晶

• 发表时间: 2004
• 期刊: Crystallogr D Biol Crystallogr 60
• 作者: Matsui T;Hogetsu K;Akao Y;Tanaka M;Sato T;Kumasaka T;Tanaka N
• 通讯作者: Tanaka N

福典之, 田中雅嗣: "肥満に関連するミトコンドリアゲノム-塩基多型の発見"医学のあゆみ. 205. 420-421 (2003)

Noriyuki Fuku、Masatsugu Tanaka：“与肥胖相关的线粒体基因组 - 核苷酸多态性的发现”《医学史》205. 420-421 (2003)。