Goals: To establish the relevance of variants in the IL-23R and ATG16L1 genes in inflammatory bowel disease (IBD).
Aim: 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.