TY - JOUR T1 - Genetic variants in the region harbouring <em>IL2/IL21</em> associated with ulcerative colitis JF - Gut JO - Gut SP - 799 LP - 804 DO - 10.1136/gut.2008.166918 VL - 58 IS - 6 AU - E A M Festen AU - P Goyette AU - R Scott AU - V Annese AU - A Zhernakova AU - J Lian AU - C Lefèbvre AU - S R Brant AU - J H Cho AU - M S Silverberg AU - K D Taylor AU - D J de Jong AU - P C Stokkers AU - D Mcgovern AU - O Palmieri AU - J-P Achkar AU - R J Xavier AU - M J Daly AU - R H Duerr AU - C Wijmenga AU - R K Weersma AU - J D Rioux Y1 - 2009/06/01 UR - http://gut.bmj.com/content/58/6/799.abstract N2 - 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 = 1.35×10−10, rs13119723 p = 8.60×10−8, rs6840978 p = 3.07×10−8, rs6822844 p = 2.77×10−9). A moderate association with CD was also found in the pooled analysis (p value range 0.0016–9.86×10−5).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. ER -