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.

我们的目标是通过使用参与 2 型糖尿病和代谢综合征发病机制的人体组织进行表达分析来阐明遗传结构。从接受胃手术的患者体内获得内脏和皮下脂肪组织的配对组织样本。表达分析显示，调整体重指数（BMI）后，瘦素基因表达水平与BMI呈正相关，脂联素基因表达水平与BMI呈负相关。主成分分析显示内脏脂肪的基因表达谱与皮下脂肪的基因表达谱明显不同，这使我们能够从基因表达数据集中预测样本的来源。我们观察到内脏脂肪组织中多个基因的表达水平显着增加了5倍，并且与皮下脂肪中的表达水平相比显着增加(P<10^<-6>)，皮下脂肪中富含参与炎症反应的基因。这些结果表明，就转录组水平的改变而言，内脏脂肪的积累在代谢综合征和2型糖尿病的发展中发挥着重要作用。

项目成果

Construction of a prediction model for type 2 diabetes mellitus in the Japanese population based on 11 genes with strong evidence of the association.

基于 11 个有强有力证据证明相关性的基因，构建了日本人群 2 型糖尿病的预测模型。

• 发表时间: 2009
• 作者: Miyake K; Yang W; Hara K; et al.
• 通讯作者: et al.

Meta-analysis of genome-wide asso- ciation 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
• 作者: Cho YS; Yamauchi T; Hara K; Kadowaki T
• 通讯作者: Kadowaki T

Regulatory polymorphism in transcription factor KLF5 at the MEF2 element alters the response to angiotensin II and is associated with human hyoertension.

MEF2 元件处转录因子 KLF5 的调节多态性会改变对血管紧张素 II 的反应，并与人类高血压相关。

• 发表时间: 2010
• 作者: Oishi Y; Manabe I; Imai Y; et al.
• 通讯作者: et al.

East Asian Genome-wide association study derived loci in relation to type 2 diabetes in the Han Chinese population.

东亚全基因组关联研究得出与中国汉族人群 2 型糖尿病相关的基因座。

• DOI: 10.18388/abp.2018_2632
• 发表时间: 2019-05-30
• 期刊: Acta biochimica Polonica
• 影响因子: 1.7
• 作者: Sijia Zhang;Esma Jamaspishvili;Huixin Tong;Yongjie Chen;Zhongyu Zhou;Lulu Sun;E. Kazakova;Qiao Hong
• 通讯作者: Qiao Hong

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（图表）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
• 影响因子: 3.5
• 作者: Imamura M; Maeda S; Yamauchi T; Hara K; Yasuda K; Morizono T; Takahashi A; Horikoshi M; Nakamura M; Fujita H; Tsunoda T; Kubo M; Watada H; Maegawa H; Okada
• 通讯作者: Okada