Clarification of genetic architecture of type 2 diabetes using expression analysis

使用表达分析阐明 2 型糖尿病的遗传结构

• 批准号: 21591124
• 负责人: HARA Kazuo
• 金额: $ 3.08万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21591124/
• 关键词: 脂肪細胞; インスリン抵抗性; 遺伝子多型; メタボリックシンドローム; 遺伝子発現

We aim to clarify genetic architecture by expression analyses using human tissues which are involved in pathogenesis of type 2 diabetes and metabolic syndrome. Paired tissue samples of visceral and subcutaneous adipose tissues were obtained from patients undergone gastric surgery. Expression analysis revealed leptin gene expression level was positively correlated with BMI and adiponectin gene expression level was negatively associated with BMI after adjustment for body mass index(BMI). Principal component analysis showed gene expression profile of visceral fat was clearly distinguished from that of subcutaneous fat, which allowed us to predict origin of sample from gene expression data set. We observed expression levels of multiple genes in visceral fat tissue were substantially increased by 5 fold and significantly increased(P<10^<-6>) compared to those in subcutaneous fat, which were enriched in genes involved in inflammatory responses. These results suggest that accumulation of visceral fat play an important role in development of metabolic syndrome and type 2 diabetes in terms of alteration in transcriptome level.

我们的目的是通过对2型糖尿病和代谢综合征发病机制中所涉及的人体组织进行表达分析来阐明遗传结构。内脏和皮下脂肪组织的配对组织样品从经历胃手术的患者获得。表达分析显示瘦素基因表达水平与BMI呈正相关，脂联素基因表达水平与校正体重指数（BMI）后的BMI呈负相关。主成分分析显示内脏脂肪和皮下脂肪的基因表达谱明显不同，这使得我们能够从基因表达数据集预测样品的来源。我们观察到内脏脂肪组织中多个基因的表达水平与皮下脂肪中的表达水平相比大幅增加了5倍，并且显著增加（P&lt;10^<-6>），皮下脂肪中富含参与炎症反应的基因。这些结果表明，内脏脂肪的积累在代谢综合征和2型糖尿病的发展中起着重要作用，在转录组水平的改变方面。

项目成果

全ゲノム遺伝子発現解析をもとにした新規2型糖尿病遺伝子の同定

基于全基因组基因表达分析鉴定新型2型糖尿病基因

• 发表时间: 2010
• 作者: 泉田欣彦;矢作直也;武内謙憲;西真貴子;宝田亜矢子;升田紫;久保田みどり;新島旭;山田哲也;片桐秀樹;岡芳知;山田信博;島野仁;門脇孝;原一雄
• 通讯作者: 原一雄

CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity

• DOI: 10.1038/nm.1964
• 发表时间: 2009-08-01
• 期刊: NATURE MEDICINE
• 影响因子: 82.9
• 作者: Nishimura, Satoshi;Manabe, Ichiro;Nagai, Ryozo
• 通讯作者: Nagai, Ryozo

A genome-wide association study in the Japanese population identifies susceptibility loci for type 2 diabetes at UBE2E2 and C2CD4A-C2CD4B

• DOI: 10.1038/ng.660
• 发表时间: 2010-10-01
• 期刊: NATURE GENETICS
• 影响因子: 30.8
• 作者: Yamauchi, Toshimasa;Hara, Kazuo;Kadowaki, Takashi
• 通讯作者: Kadowaki, Takashi

Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians.

全基因组关联研究的荟萃分析确定了东亚人 2 型糖尿病的 8 个新位点

• DOI: 10.1038/ng.1019
• 发表时间: 2011-12-11
• 期刊: NATURE GENETICS
• 影响因子: 30.8
• 作者: Cho, Yoon Shin;Chen, Chien-Hsiun;Hu, Cheng;Long, Jirong;Ong, Rick Twee Hee;Sim, Xueling;Takeuchi, Fumihiko;Wu, Ying;Go, Min Jin;Yamauchi, Toshimasa;Chang, Yi-Cheng;Kwak, Soo Heon;Ma, Ronald C. W.;Yamamoto, Ken;Adair, Linda S.;Aung, Tin;Cai, Qiuyin;Chang, Li-Ching;Chen, Yuan-Tsong;Gao, Yutang;Hu, Frank B.;Kim, Hyung-Lae;Kim, Sangsoo;Kim, Young Jin;Lee, Jeannette Jen-Mai;Lee, Nanette R.;Li, Yun;Liu, Jian Jun;Lu, Wei;Nakamura, Jiro;Nakashima, Eitaro;Ng, Daniel Peng-Keat;Tay, Wan Ting;Tsai, Fuu-Jen;Wong, Tien Yin;Yokota, Mitsuhiro;Zheng, Wei;Zhang, Rong;Wang, Congrong;So, Wing Yee;Ohnaka, Keizo;Ikegami, Hiroshi;Hara, Kazuo;Cho, Young Min;Cho, Nam H.;Chang, Tien-Jyun;Bao, Yuqian;Hedman, Asa K.;Morris, Andrew P.;McCarthy, Mark I.;Takayanagi, Ryoichi;Park, Kyong Soo;Jia, Weiping;Chuang, Lee-Ming;Chan, Juliana C. N.;Maeda, Shiro;Kadowaki, Takashi;Lee, Jong-Young;Wu, Jer-Yuarn;Teo, Yik Ying;Tai, E. Shyong;Shu, Xiao Ou;Mohlke, Karen L.;Kato, Norihiro;Han, Bok-Ghee;Seielstad, Mark
• 通讯作者: Seielstad, Mark

Diabetes Genetics Replication and Meta-analysis (DIAGRAM) Consortium, Nakamura Y, Kadowaki T: A single-nucleotide polymorphism in ANK1 is associated with susceptibility to type 2 diabetes in Japanese populations

糖尿病遗传学复制和荟萃分析 (DIAGRAM) 联盟、Nakamura Y、Kadowaki T：ANK1 中的单核苷酸多态性与日本人群对 2 型糖尿病的易感性相关

• 发表时间: 2012
• 期刊: Human Molecular Genatics
• 作者: Imamura M,1,Yamauchi T;Hara K;Okada-Iwabu M;Iwabu M
• 通讯作者: Iwabu M