生物谷报道：糖尿病患者一级亲属发生糖尿病的几率为普通人群的3.5倍,说明糖尿病与遗传密切相关。近日,美国和欧洲多个基因研究组织确认了3个与糖尿病相关的新基因位点。(Science 2007年6月1日)
该研究采用全基因组分析法对1464例2型糖尿病患者和1467例糖耐量正常个体的基因结构进行了系统研究,共分析了与糖代谢、脂质、肥胖和血压调节相关的386731个常见的单核苷酸多态性(SNP)位点。
结果显示,共发现3个与糖尿病发病相关的新基因位点。这三个位点分别是:位于9号染色体临近CDKN2A/CDKN2B的非编码区、3号染色体IGF2BP2和CDKAL1,同时肯定了先前发现的与2型糖尿病危险相关的6个基因位点:TCF7L2、SLC30A8、HHEX、PPARG、KCNJ11和FTO,并确认葡萄糖激酶调节蛋白内含子的一个SNP位点与血浆甘油三酯水平相关。应用已发现的基因变异位点创建的logistic回归模型显示,存在遗传变异的受试者发生糖尿病的危险增高4倍。
原始出处:
Originally published in Science Express on 26 April 2007
Science 1 June 2007:
Vol. 316. no. 5829, pp. 1341 - 1345
DOI: 10.1126/science.1142382
A Genome-Wide Association Study of Type 2 Diabetes in Finns Detects Multiple Susceptibility Variants
Laura J. Scott,1 Karen L. Mohlke,2 Lori L. Bonnycastle,3 Cristen J. Willer,1 Yun Li,1 William L. Duren,1 Michael R. Erdos,3 Heather M. Stringham,1 Peter S. Chines,3 Anne U. Jackson,1 Ludmila Prokunina-Olsson,3 Chia-Jen Ding,1 Amy J. Swift,3 Narisu Narisu,3 Tianle Hu,1 Randall Pruim,4 Rui Xiao,1 Xiao-Yi Li,1 Karen N. Conneely,1 Nancy L. Riebow,3 Andrew G. Sprau,3 Maurine Tong,3 Peggy P. White,1 Kurt N. Hetrick,5 Michael W. Barnhart,5 Craig W. Bark,5 Janet L. Goldstein,5 Lee Watkins,5 Fang Xiang,1 Jouko Saramies,6 Thomas A. Buchanan,7 Richard M. Watanabe,8,9 Timo T. Valle,10 Leena Kinnunen,10,11 Gonçalo R. Abecasis,1 Elizabeth W. Pugh,5 Kimberly F. Doheny,5 Richard N. Bergman,9 Jaakko Tuomilehto,10,11,12 Francis S. Collins,3* Michael Boehnke1*
Identifying the genetic variants that increase the risk of type 2 diabetes (T2D) in humans has been a formidable challenge. Adopting a genome-wide association strategy, we genotyped 1161 Finnish T2D cases and 1174 Finnish normal glucose-tolerant (NGT) controls with >315,000 single-nucleotide polymorphisms (SNPs) and imputed genotypes for an additional >2 million autosomal SNPs. We carried out association analysis with these SNPs to identify genetic variants that predispose to T2D, compared our T2D association results with the results of two similar studies, and genotyped 80 SNPs in an additional 1215 Finnish T2D cases and 1258 Finnish NGT controls. We identify T2D-associated variants in an intergenic region of chromosome 11p12, contribute to the identification of T2D-associated variants near the genes IGF2BP2 and CDKAL1 and the region of CDKN2A and CDKN2B, and confirm that variants near TCF7L2, SLC30A8, HHEX, FTO, PPARG, and KCNJ11 are associated with T2D risk. This brings the number of T2D loci now confidently identified to at least 10.
1 Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
2 Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
3 Genome Technology Branch, National Human Genome Research Institute, Bethesda, MD 20892, USA.
4 Department of Mathematics and Statistics, Calvin College, Grand Rapids, MI 49546, USA.
5 Center for Inherited Disease Research (CIDR), Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21224, USA.
6 Savitaipale Health Center, 54800 Savitaipale, Finland.
7 Division of Endocrinology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
8 Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
9 Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
10 Diabetes Unit, Department of Epidemiology and Health Promotion, National Public Health Institute, 00300 Helsinki, Finland.
11 Department of Public Health, University of Helsinki, 00014 Helsinki, Finland.
12 South Ostrobothnia Central Hospital, 60220 Seinäjoki, Finland.
* To whom correspondence should be addressed. E-mail: boehnke@umich.edu (M.B.); francisc@mail.nih.gov (F.S.C.)
