Expression analysis of loci associated with type 2 diabetes in human tissues.
Expression analysis of loci associated with type 2 diabetes in human tissues.
复制标题
DOI：
10.1007/s00125-010-1861-2
复制
发表时间：
2010-11
期刊：
影响因子：
8.2
通讯作者：
Hall, J. L.
中科院分区：
文献类型：
--
作者：
Cotsapas, C.;Prokunina-Olsson, L.;Welch, C.;Saxena, R.;Weaver, C.;Usher, N.;Guiducci, C.;Bonakdar, S.;Turner, N.;LaCroix, B.;Hall, J. L.
基因图谱已确定了超过 20 个与 2 型糖尿病遗传风险相关的基因座。下一步是确定调节遗传风险对疾病的影响的基因和机制。本研究的目的是评估年龄、身高、体重和风险等位基因对三种相关人体组织中糖尿病相关区域候选基因表达的影响。我们通过定量 RT-PCR 测量了人胰腺 (n=50)、结肠 (n=195) 和肝脏 (n=50) 中 WFS1、KCNJ11、TCF2（也称为 HNF1B）、PPARG、HHEX、IDE、CDKAL1、CDKN2A、CDKN2B、IGF2BP2、SLC30A8 和 TCF7L2 的转录本丰度。对组织样本进行与 2 型糖尿病相关的单核苷酸多态性 (SNP) 基因分型。通过线性模型测试年龄、身高、体重、组织和SNP对RNA表达的影响。所有基因的表达都表现出组织偏差。免疫组织化学证实了 HHEX、IDE 和 SLC30A8 的研究结果，显示出最强的组织特异性 mRNA 表达偏差。年龄、身高和体重均与基因表达无关。我们没有发现任何证据表明 2 型糖尿病相关的 SNP 会影响结肠、胰腺和肝脏中的邻近基因表达（顺式表达数量性状位点）。这项研究提供了新的证据，表明与 2 型糖尿病风险增加相关的候选基因中或附近的组织类型，而不是年龄、身高、体重或 SNP，是所检查基因和组织中基因表达差异的重要因素。
Genetic mapping has identified over 20 loci contributing to genetic risk of type 2 diabetes. The next step is to identify the genes and mechanisms regulating the contributions of genetic risk to disease. The goal of this study was to evaluate the effect of age, height, weight and risk alleles on expression of candidate genes in diabetes-associated regions in three relevant human tissues. We measured transcript abundance for WFS1, KCNJ11, TCF2 (also known as HNF1B), PPARG, HHEX, IDE, CDKAL1, CDKN2A, CDKN2B, IGF2BP2, SLC30A8 and TCF7L2 by quantitative RT-PCR in human pancreas (n=50), colon (n=195) and liver (n=50). Tissue samples were genotyped for single nucleotide polymorphisms (SNPs) associated with type 2 diabetes. The effects of age, height, weight, tissue and SNP on RNA expression were tested by linear modelling. Expression of all genes exhibited tissue bias. Immunohistochemistry confirmed the findings for HHEX, IDE and SLC30A8, which showed strongest tissue-specific mRNA expression bias. Neither age, height nor weight were associated with gene expression. We found no evidence that type 2 diabetes-associated SNPs affect neighbouring gene expression (cis-expression quantitative trait loci) in colon, pancreas and liver. This study provides new evidence that tissue-type, but not age, height, weight or SNPs in or near candidate genes associated with increased risk of type 2 diabetes are strong contributors to differential gene expression in the genes and tissues examined.
登录
查看更多内容
影响因子：
64.8
作者：
Frazer, Kelly A.;Ballinger, Dennis G.;Cox, David R.;Hinds, David A.;Stuve, Laura L.;Gibbs, Richard A.;Belmont, John W.;Boudreau, Andrew;Hardenbol, Paul;Leal, Suzanne M.;Pasternak, Shiran;Wheeler, David A.;Willis, Thomas D.;Yu, Fuli;Yang, Huanming;Zeng, Changqing;Gao, Yang;Hu, Haoran;Hu, Weitao;Li, Chaohua;Lin, Wei;Liu, Siqi;Pan, Hao;Tang, Xiaoli;Wang, Jian;Wang, Wei;Yu, Jun;Zhang, Bo;Zhang, Qingrun;Zhao, Hongbin;Zhao, Hui;Zhou, Jun;Gabriel, Stacey B.;Barry, Rachel;Blumenstiel, Brendan;Camargo, Amy;Defelice, Matthew;Faggart, Maura;Goyette, Mary;Gupta, Supriya;Moore, Jamie;Nguyen, Huy;Onofrio, Robert C.;Parkin, Melissa;Roy, Jessica;Stahl, Erich;Winchester, Ellen;Ziaugra, Liuda;Altshuler, David;Shen, Yan;Yao, Zhijian;Huang, Wei;Chu, Xun;He, Yungang;Jin, Li;Liu, Yangfan;Shen, Yayun;Sun, Weiwei;Wang, Haifeng;Wang, Yi;Wang, Ying;Xiong, Xiaoyan;Xu, Liang;Waye, Mary M. Y.;Tsui, Stephen K. W.;Wong, J. Tze-Fei;Galver, Luana M.;Fan, Jian-Bing;Gunderson, Kevin;Murray, Sarah S.;Oliphant, Arnold R.;Chee, Mark S.;Montpetit, Alexandre;Chagnon, Fanny;Ferretti, Vincent;Leboeuf, Martin;Olivier, Jean-Franccois;Phillips, Michael S.;Roumy, Stephanie;Sallee, Clementine;Verner, Andrei;Hudson, Thomas J.;Kwok, Pui-Yan;Cai, Dongmei;Koboldt, Daniel C.;Miller, Raymond D.;Pawlikowska, Ludmila;Taillon-Miller, Patricia;Xiao, Ming;Tsui, Lap-Chee;Mak, William;Song, You Qiang;Tam, Paul K. H.;Nakamura, Yusuke;Kawaguchi, Takahisa;Kitamoto, Takuya;Morizono, Takashi;Nagashima, Atsushi;Ohnishi, Yozo;Sekine, Akihiro;Tanaka, Toshihiro;Tsunoda, Tatsuhiko;Deloukas, Panos;Bird, Christine P.;Delgado, Marcos;Dermitzakis, Emmanouil T.;Gwilliam, Rhian;Hunt, Sarah;Morrison, Jonathan;Powell, Don;Stranger, Barbara E.;Whittaker, Pamela;Bentley, David R.;Daly, Mark J.;de Bakker, Paul I. W.;Barrett, Jeff;Chretien, Yves R.;Maller, Julian;McCarroll, Steve;Patterson, Nick;Pe'er, Itsik;Price, Alkes;Purcell, Shaun;Richter, Daniel J.;Sabeti, Pardis;Saxena, Richa;Schaffner, Stephen F.;Sham, Pak C.;Varilly, Patrick;Altshuler, David;Stein, Lincoln D.;Krishnan, Lalitha;Smith, Albert Vernon;Tello-Ruiz, Marcela K.;Thorisson, Gudmundur A.;Chakravarti, Aravinda;Chen, Peter E.;Cutler, David J.;Kashuk, Carl S.;Lin, Shin;Abecasis, Goncalo R.;Guan, Weihua;Li, Yun;Munro, Heather M.;Qin, Zhaohui Steve;Thomas, Daryl J.;McVean, Gilean;Auton, Adam;Bottolo, Leonardo;Cardin, Niall;Eyheramendy, Susana;Freeman, Colin;Marchini, Jonathan;Myers, Simon;Spencer, Chris;Stephens, Matthew;Donnelly, Peter;Cardon, Lon R.;Clarke, Geraldine;Evans, David M.;Morris, Andrew P.;Weir, Bruce S.;Tsunoda, Tatsuhiko;Johnson, Todd A.;Mullikin, James C.;Sherry, Stephen T.;Feolo, Michael;Skol, Andrew
通讯作者：
Skol, Andrew
影响因子：
7.7
作者：
Chimienti, F;Devergnas, S;Seve, M
通讯作者：
Seve, M
人类基因表达的群体基因组学。
影响因子：
30.8
作者：
通讯作者：
--
TCF7L2的组织特异性替代剪接。
影响因子：
3.5
作者：
Prokunina-Olsson, Ludmila;Welch, Cullan;Hansson, Ola;Adhikari, Neeta;Scott, Laura J.;Usher, Nicolle;Tong, Maurine;Sprau, Andrew;Swift, Amy;Bonnycastle, Lori L.;Erdos, Michael R.;He, Zhi;Saxena, Richa;Harmon, Brennan;Kotova, Olga;Hoffman, Eric P.;Altshuler, David;Groop, Leif;Boehnke, Michael;Collins, Francis S.;Hall, Jennifer L.
通讯作者：
Hall, Jennifer L.
DOI：
10.1007/978-1-60761-247-6_17
发表时间：
2009-01-01
期刊：
CARDIOVASCULAR GENOMICS: METHODS AND PROTOCOLS
影响因子：
--
作者：
Franke, Lude;Jansen, Ritsert C.
通讯作者：
Jansen, Ritsert C.