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

E. A M Festen, 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. WijmengaR. K. Weersma, J. D. Rioux

Research output: Contribution to journalArticle

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 = 1.35×10-10, 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.

Original languageEnglish
Pages (from-to)799-804
Number of pages6
JournalGut
Volume58
Issue number6
DOIs
Publication statusPublished - Jun 2009

ASJC Scopus subject areas

  • Gastroenterology

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    Festen, E. A. M., Goyette, P., Scott, R., Annese, V., Zhernakova, A., Lian, J., Lefèbvre, C., Brant, S. R., Cho, J. H., Silverberg, M. S., Taylor, K. D., De Jong, D. J., Stokkers, P. C., Mcgovern, D., Palmieri, O., Achkar, J. P., Xavier, R. J., Daly, M. J., Duerr, R. H., ... Rioux, J. D. (2009). Genetic variants in the region harbouring IL2/IL21 associated with ulcerative colitis. Gut, 58(6), 799-804. https://doi.org/10.1136/gut.2008.166918