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.
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Competing interests: None.
Funding: This study was made possible by a VICI grant from the Netherlands Organization for Scientific Research (918.66.620) to CW, and an AGIKO-grant from the Netherlands Organization for Scientific Research to EF.
▸ Additional tables are published online only at http://gut.bmj.com/content/vol58/issue6
Patient consent: Informed consent was obtained using protocols approved by the local institutional review board in all participating institutions.
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