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.
Genetic variants in the region harbouring IL2/IL21 associated with ulcerative colitis / Festen, E. A. M.; Goyette, P.; Scott, R.; Annese, V.; Zhernakova, A.; Lian, J.; Lefebvre, 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.; Wijmenga, C.; Weersma, R. K.; Rioux, J. D.. - In: GUT. - ISSN 0017-5749. - 58:6(2009), pp. 799-804. [10.1136/gut.2008.166918]
Genetic variants in the region harbouring IL2/IL21 associated with ulcerative colitis
Annese V.;
2009-01-01
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.