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

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
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.
[J]. 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
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
[J]. AMERICAN JOURNAL OF HUMAN GENETICS, 2007, 81 (06) : 1284 - 1288

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