ATG16L1 and IL23R are associated with inflammatory bowel diseases but not with celiac disease in the Netherlands.
BACKGROUND
Inflammatory bowel disease (IBD)--Crohn's disease (CD) and ulcerative colitis (UC)--and celiac disease are intestinal inflammatory disorders with a complex genetic background. Recently, two novel genes were found to be associated with IBD susceptibility. One, an uncommon coding variant (rs11209026) in the gene encoding for the interleukin-23 receptor (IL23R), conferred strong protection against CD. The other, rs2241880 in the autophagy-related 16-like 1 gene (ATG16L1), was associated with CD. We performed a case-control study for the association of IBD with IL23R and ATG16L1 in a Dutch cohort. We also looked at the association of IL23R and ATG16L1 with celiac disease.


METHODS
Five hundred eighteen Dutch white IBD patients (311 CD and 207 UC, including 176 trios of patients with both parents), 508 celiac disease patients, and 893 healthy controls were studied for association with the rs11209026 (IL23R) and rs2241880 (ATG16L1) single nucleotide polymorphisms (SNP).


RESULTS
The rs11209026 SNP in IL23R had a protective effect for IBD in the case-control analysis (odds ratio [OR] 0.19, 95% confidence interval [CI] 0.10-0.37, P= 6.6E-09). Both CD (OR 0.14, CI 0.06-0.37, P= 3.9E-07) and UC (OR 0.33, CI 0.15-0.73, P= 1.4E-03) were associated with IL23R. For ATG16L1, the rs2241880 SNP was associated with CD susceptibility (OR 1.36, CI 1.12-1.66, P= 0.0017). The population-attributable risk of carrying allele G is 0.24 and is 0.19 for homozygosity for allele G in CD. No association was found between IL23R or ATG16L1 and celiac disease.


CONCLUSIONS
We confirmed the association of IL23R and ATG16L1 with CD susceptibility and also the association of IL23R with UC. We found IL23R and ATG16L1 were not associated with celiac disease susceptibility.
Department of Gastroenterology and Hepatology, University Medical Center Groningen, The Netherlands.
Rinse K
RK
Weersma
Alexandra
A
Zhernakova
Ilja M
IM
Nolte
Céline
C
Lefebvre
John D
JD
Rioux
Flip
F
Mulder
Hendrik M
HM
van Dullemen
Jan H
JH
Kleibeuker
Cisca
C
Wijmenga
Gerard
G
Dijkstra
D000293:Adolescent; D000328:Adult; D000368:Aged; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D002446:Celiac Disease / Q000235:genetics*; D002648:Child; D003093:Colitis, Ulcerative / Q000235:genetics*; D003424:Crohn Disease / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D020641:Polymorphism, Single Nucleotide; D018123:Receptors, Interleukin / Q000235:genetics*
C518959:ATG16L1 protein, human; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D005819:Genetic Markers; C515500:IL23R protein, human; D018123:Receptors, Interleukin