Genetic variants in the region harbouring IL2/IL21 associated with ulcerative colitis

被引:116
作者
Festen, E. A. M. [2 ]
Goyette, P. [1 ]
Scott, R. [3 ]
Annese, V. [4 ]
Zhernakova, A. [5 ]
Lian, J. [1 ]
Lefebvre, C. [1 ]
Brant, S. R. [6 ]
Cho, J. H. [7 ,8 ]
Silverberg, M. S. [9 ]
Taylor, K. D. [10 ,11 ]
de Jong, D. J. [12 ]
Stokkers, P. C. [13 ]
Mcgovern, D. [13 ]
Palmieri, O. [4 ]
Achkar, J-P [14 ]
Xavier, R. J. [15 ,16 ]
Daly, M. J. [17 ]
Duerr, R. H. [3 ]
Wijmenga, C. [1 ]
Weersma, R. K. [2 ]
Rioux, J. D. [1 ]
机构
[1] Univ Montreal, Montreal Heart Inst, Lab Genet & Genom Med Inflammat, Montreal, PQ H1T 1C8, Canada
[2] Univ Groningen, Univ Med Ctr Groningen, Dept Gastroenterol & Hepatol, Groningen, Netherlands
[3] Univ Pittsburgh, Sch Med, Dept Med, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA
[4] IRCCS, UU OO Gastroenterol & Endoscopia Digest, Osped Casa Sollievo Sofferenza, San Giovanni Rotondo, Italy
[5] Univ Med Ctr Utrecht, Dept Med Genet, Complex Genet Sect, Utrecht, Netherlands
[6] Johns Hopkins Univ, Dept Med, Harvey M & Lyn P Meyerhoff Inflammatory Bowel Dis, Baltimore, MD USA
[7] Yale Univ, Dept Med, Div Gastroenterol, Inflammatory Bowel Dis IBD Ctr, New Haven, CT 06520 USA
[8] Yale Univ, Dept Genet, Div Gastroenterol, Inflammatory Bowel Dis IBD Ctr, New Haven, CT 06520 USA
[9] Univ Toronto, Mt Sinai Hosp, IBD Ctr, Toronto, ON M5G 1X5, Canada
[10] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA
[11] Cedars Sinai Med Ctr, Inflammatory Bowel Dis IBD Ctr, Los Angeles, CA 90048 USA
[12] Radboud Univ Nijmegen, Med Ctr, Dept Gastroenterol & Hepatol, NL-6525 ED Nijmegen, Netherlands
[13] Univ Amsterdam, Acad Med Ctr, Dept Gastroenterol & Hepatol, NL-1105 AZ Amsterdam, Netherlands
[14] Cleveland Clin, Ctr Inflammatory Bowel Dis, Dept Gastroenterol & Hepatol, Cleveland, OH 44106 USA
[15] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Cambridge, MA 02138 USA
[16] Harvard Univ, Ctr Computat & Integrat Biol, Sch Med, Cambridge, MA 02138 USA
[17] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA
关键词
GENOME-WIDE ASSOCIATION; INFLAMMATORY-BOWEL-DISEASE; SYSTEMIC-LUPUS-ERYTHEMATOSUS; CELIAC-DISEASE; CROHNS-DISEASE; SUSCEPTIBILITY LOCI; BARRIER DEFECT; RISK VARIANTS; MYOSIN IXB; INTERLEUKIN-21;
D O I
10.1136/gut.2008.166918
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Objectives: Genetic susceptibility is known to play a large part in the predisposition to the inflammatory bowel diseases (IBDs) known as Crohn's disease (CD) and ulcerative colitis (UC). The IL2/IL21 locus on 4q27 is known to be a common risk locus for inflammatory disease (shown in coeliac disease, type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus and psoriasis), while the roles that interleukin 2 (IL2) and IL21 play in the immune response also make them attractive candidates for IBD. The objective of this study was to test for association between the IL2/IL21 locus and the IBDs. Methods: The four single nucleotide polymorphisms (SNPs) in the IL2/IL21 locus most associated with coeliac disease were genotyped in 1590 subjects with IBD and 929 controls from The Netherlands, and then replicated in a North American cohort (2387 cases and 1266 controls) and an Italian cohort (805 cases and 421 controls), yielding a total of 4782 cases (3194 UC, 1588 CD) and 2616 controls. Allelic association testing and a pooled analysis using a Cochran-Mantel-Haenszel test were performed. Results: All four SNPs were strongly associated with UC in all three cohorts and reached genome-wide significance in the pooled analysis (rs13151961 p = 1.35x10(-10), rs13119723 p = 8.60x10(-8), rs6840978 p = 3.07x10(-8), rs6822844 p = 2.77x10(-9)). A moderate association with CD was also found in the pooled analysis (p value range 0.0016-9.86x10(-5)). Conclusions: A strong association for the IL2/IL21 locus with UC was found, which also confirms it as a general susceptibility locus for inflammatory disease.
引用
收藏
页码:799 / 804
页数:6
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