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. 2009 Jun;58(6):799-804.
doi: 10.1136/gut.2008.166918. Epub 2009 Feb 6.

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

E A M Festen  1 , P Goyette, R Scott, V Annese, A Zhernakova, J Lian, C Lefèbvre, S R Brant, J H Cho, M S Silverberg, K D Taylor, D J de Jong, P C Stokkers, D Mcgovern, O Palmieri, J-P Achkar, R J Xavier, M J Daly, R H Duerr, C Wijmenga, R K Weersma, J D Rioux
Affiliations

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

E A M Festen et al. Gut. 2009 Jun.

Abstract

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 = 1.35 x 10(-10), rs13119723 p = 8.60 x 10(-8), rs6840978 p = 3.0 7x 10(-8), rs6822844 p = 2.77 x 10(-9)). A moderate association with CD was also found in the pooled analysis (p value range 0.0016-9.86 x 10(-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.

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Conflict of interest statement

Authors’ disclosure: No authors have a conflict of interest to declare.

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