title: Genetic variants in the region harbouring IL2/IL21 associated with ulcerative colitis.
abstract: OBJECTIVE
  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 x 10(-10), rs13119723 p = 8.60 x 10(-8), rs6840978 p = 3.0 7x 10(-8), rs6822844 p = 2.77 x 10(-9)). A moderate association with CD was also found in the pooled analysis (p value range 0.0016-9.86 x 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.
authors.affiliation: Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: E A M
authors.initials: EA
authors.lastname: Festen
authors.forename: P
authors.initials: P
authors.lastname: Goyette
authors.forename: R
authors.initials: R
authors.lastname: Scott
authors.forename: V
authors.initials: V
authors.lastname: Annese
authors.forename: A
authors.initials: A
authors.lastname: Zhernakova
authors.forename: J
authors.initials: J
authors.lastname: Lian
authors.forename: C
authors.initials: C
authors.lastname: Lefèbvre
authors.forename: S R
authors.initials: SR
authors.lastname: Brant
authors.forename: J H
authors.initials: JH
authors.lastname: Cho
authors.forename: M S
authors.initials: MS
authors.lastname: Silverberg
authors.forename: K D
authors.initials: KD
authors.lastname: Taylor
authors.forename: D J
authors.initials: DJ
authors.lastname: de Jong
authors.forename: P C
authors.initials: PC
authors.lastname: Stokkers
authors.forename: D
authors.initials: D
authors.lastname: Mcgovern
authors.forename: O
authors.initials: O
authors.lastname: Palmieri
authors.forename: J-P
authors.initials: JP
authors.lastname: Achkar
authors.forename: R J
authors.initials: RJ
authors.lastname: Xavier
authors.forename: M J
authors.initials: MJ
authors.lastname: Daly
authors.forename: R H
authors.initials: RH
authors.lastname: Duerr
authors.forename: C
authors.initials: C
authors.lastname: Wijmenga
authors.forename: R K
authors.initials: RK
authors.lastname: Weersma
authors.forename: J D
authors.initials: JD
authors.lastname: Rioux
mesh_terms: D016009:Chi-Square Distribution; D003093:Colitis, Ulcerative / Q000235:genetics*; D003424:Crohn Disease / Q000235:genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics*; D007378:Interleukins / Q000235:genetics*; D007558:Italy; D009426:Netherlands; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D014481:United States; D000098546:Interleukin-21
chemical_list: D007376:Interleukin-2; D007378:Interleukins; D000098546:Interleukin-21