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

• Published in: Gut Vol. 58; no. 6; pp. 799 - 804
• Main Authors: 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, Wijmenga, C, Weersma, R K, Rioux, J D
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and British Society of Gastroenterology 01.06.2009; BMJ Publishing Group; BMJ Publishing Group LTD
• Subjects: Abdomen; Biological and medical sciences; Celiac disease; Chi-Square Distribution; Colitis, Ulcerative - genetics; Crohn Disease - genetics; Cytokines; Diabetes; Gastroenterology. Liver. Pancreas. Abdomen; Gene Frequency; Genes; Genetic Predisposition to Disease; Genome-Wide Association Study; Genomes; Genotype; Humans; Inflammation; Inflammatory bowel disease; Inflammatory diseases; Interleukin-2 - genetics; Interleukin-21; Interleukins - genetics; Italy; Lupus; Medical sciences; Netherlands; Odds Ratio; Other diseases. Semiology; Pathogenesis; Polymorphism, Single Nucleotide; Psoriasis; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Studies; United States; Genetic variant; Gastroenterology; Interleukin 21; Digestive diseases; Intestinal disease; Inflammatory disease; Ulcerative colitis
• ISSN: 0017-5749; 1468-3288; 1468-3288
• DOI: 10.1136/gut.2008.166918

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.