Autophagy Gene ATG16L1 But Not IRGM Is Associated with Crohn's Disease in Canadian Children

Background: Recent genome-wide studies, have implicated the autophagy genes ATG16L1 and IRGM in the pathogenesis of Crohn's disease (CD). We investigated, whether these genes were associated with CID in Canadian children. Methods: A case-control Study was carried Out at 2 pediatric gastroenterology, clinics in Canada. Continued cases of CD <20 years diagnosed using standard criteria were classified according to the Montreal Classification scheme. Single nucleotide polymorphisms (SNPs) rs2241980 (ATG16L1) and rs10065172 (IRGM) alone with CARD15 SNPs. SNP8. SNP12, and SNP13 were, genotyped. Results: A total of 289 CD cases and 290 controls were studied. The mean age (+/-SD) of the cases was 12.1 (+/-3.5) years of age. Most cases were male (55.4%), had disease location L3 +/- L4 (56.7%). and an inflammatory phenotype B1 +/- p (87.2%) at diagnosis. rs2241880 (ATG16L1) was strongly associated with CD (allelic P = 1.24 X 10(-6)). Children with GG genotype had a more than 3-fold elevated risk for disease its compared to the wildtype AA homozygotes (odds ratio [OR], 3.1;, 95% confidence interval [CI]. 1.93-4.94: P = 1.8 x 10(-6)). Association with SNP rs2241880 was specific for deal disease (with or without colonic involvement) (case-based allelic P = 0.02; P-value Versus Controls 9.5 X 10(-8)). The frequency of IRGM SNP rs10065172 was higher in cases but differences with controls were not statistically significant. No interactions between CARD15 and either ATG16L1 or IRGM were evident. Conclusions: We have confirmed associations between CD and ATG16L1 in a pediatric cohort of Canadian children. Associations with IRGM need to be further evaluated in larger studies.