Genetic variants in IL-23R and ATG16L1 independently predispose to increased susceptibility to Crohn's disease in a Canadian population.
OBJECTIVE
To establish the relevance of variants in the IL-23R and ATG16L1 genes in inflammatory bowel disease (IBD).


OBJECTIVE
Three recent genome wide association studies have identified variants in the IL-23R and ATG16L1 genes, which modulate susceptibility to Crohn's disease (CD).


METHODS
We genotyped 1028 IBD patients, including 443 CD and 347 ulcerative colitis (UC) non-Jewish cases, 238 (183 CD and 55 UC) Jewish cases, and 1005 ethnically matched control subjects for 18 and 11 variants, respectively, in the IL-23R and ATG16L1 genes, including the IL-23R (R381Q) and ATG16L1 (T216A) variants, previously associated with CD.


RESULTS
Single nucleotide polymorphisms within each of 3 haplotype blocks across the IL-23R gene were associated with an increased risk of CD. Notably, the minor allele of the IL-23R R381Q variant was present in 2.9% of cases and 6.0% controls (P=0.0001, odds ratio=0.48, 95% confidence interval 0.33-0.69). Homozygosity for the minor (T) allele of the ATG16L1 T216A polymorphism was strongly protective for CD (P=0.0001, odds ratio=0.51, 95% confidence interval 0.38-0.68). No phenotypic associations were detected and no interactions between the genes to increase disease risk were established.


CONCLUSIONS
We confirm the association of CD with variants in the IL-23R and ATG16L1 genes and the more modest association of the IL-23R R381Q variant with UC. Our results also suggest that these variants act independently of one another to influence risk and pathogenesis of IBD.
Newman
William G
WG
Academic Department of Medical Genetics, University of Manchester, Manchester, UK.
Zhang
Qing
Q
Liu
Xiangdong
X
Amos
Christopher I
CI
Siminovitch
Katherine A
KA
D000071183:Autophagy-Related Proteins; D002170:Canada; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000208:ethnology / Q000235:genetics*; D003424:Crohn Disease / Q000208:ethnology / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007585:Jews / Q000235:genetics; D016015:Logistic Models; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D018123:Receptors, Interleukin / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D044465:White People / Q000235:genetics
C518959:ATG16L1 protein, human; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; C515500:IL23R protein, human; D018123:Receptors, Interleukin