生物谷報道：糖尿病患者一級親屬發(fā)生糖尿病的幾率為普通人群的3.5倍,說明糖尿病與遺傳密切相關,。近日,美國和歐洲多個基因研究組織確認了3個與糖尿病相關的新基因位點。(Science 2007年6月1日)
該研究采用全基因組分析法對1464例2型糖尿病患者和1467例糖耐量正常個體的基因結構進行了系統(tǒng)研究,共分析了與糖代謝,、脂質,、肥胖和血壓調節(jié)相關的386731個常見的單核苷酸多態(tài)性(SNP)位點,。
結果顯示,共發(fā)現(xiàn)3個與糖尿病發(fā)病相關的新基因位點。這三個位點分別是:位于9號染色體臨近CDKN2A/CDKN2B的非編碼區(qū),、3號染色體IGF2BP2和CDKAL1,同時肯定了先前發(fā)現(xiàn)的與2型糖尿病危險相關的6個基因位點:TCF7L2,、SLC30A8、HHEX,、PPARG,、KCNJ11和FTO,并確認葡萄糖激酶調節(jié)蛋白內含子的一個SNP位點與血漿甘油三酯水平相關。應用已發(fā)現(xiàn)的基因變異位點創(chuàng)建的logistic回歸模型顯示,存在遺傳變異的受試者發(fā)生糖尿病的危險增高4倍,。
原始出處:
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: [email protected] (M.B.); [email protected] (F.S.C.)
