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

被引：117

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

来源：

GUT | 2009年 / 58卷 / 06期

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

页码：799 / 804

页数：6

共 32 条

[31] Genetic analysis of innate immunity in Crohn's disease and ulcerative colitis identifies two susceptibility loci harboring CARD9 and IL18RAP [J].

Zhernakova, Alexandra ;

Festen, Eleanora M. ;

Franke, Lude ;

Trynka, Gosia ;

van Diemen, Cleo C. ;

Monsuur, Alienke J. ;

Bevova, Marianna ;

Nijmeijer, Rian M. ;

van't Slot, Ruben ;

Heijmans, Roel ;

Boezen, H. Marike ;

van Heel, David A. ;

van Bodegraven, Adriaan A. ;

Stokkers, Pieter C. F. ;

Wijmenga, Cisca ;

Crusius, J. Bart A. ;

Weersma, Rinse K. .

AMERICAN JOURNAL OF HUMAN GENETICS, 2008, 82 (05) :1202-1210

[32] Novel association in chromosome 4q27 region with rheumatoid arthritis and confirmation of type 1 diabetes point to a general risk locus for autoimmune diseases [J].

Zhernakova, Alexandra ;

Alizadeh, Behrooz Z. ;

Bevova, Marianna ;

van Leeuwen, Miek A. ;

Coenen, Marieke J. H. ;

Franke, Barbara ;

Franke, Lude ;

Posthumus, Marcel D. ;

van Heel, David A. ;

van der Steege, Gerrit ;

Radstake, Timothy R. D. J. ;

Barrera, Pilar ;

Roep, Bart O. ;

Koeleman, Bobby P. C. ;

Wijmenga, Cisca .

AMERICAN JOURNAL OF HUMAN GENETICS, 2007, 81 (06) :1284-1288

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