Genetic variants in the region harbouring IL2/IL21 associated with ulcerative colitis.
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.
Festen
E A M
EA
Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Goyette
P
P
Scott
R
R
Annese
V
V
Zhernakova
A
A
Lian
J
J
Lefèbvre
C
C
Brant
S R
SR
Cho
J H
JH
Silverberg
M S
MS
Taylor
K D
KD
de Jong
D J
DJ
Stokkers
P C
PC
Mcgovern
D
D
Palmieri
O
O
Achkar
J-P
JP
Xavier
R J
RJ
Daly
M J
MJ
Duerr
R H
RH
Wijmenga
C
C
Weersma
R K
RK
Rioux
J D
JD
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
D007376:Interleukin-2; D007378:Interleukins; D000098546:Interleukin-21