Replication of interleukin 23 receptor and autophagyrelated 16-like 1 association in adult- and pediatric-onset inflammatory bowel disease in Italy

AIM: To investigate gene variants in a large Italian inflammatory bowel disease (IBD) cohort, and to analyze the correlation of sub-phenotypes (including age at diagnosis) and epistatic interaction with other IBD genes.METHODS: Total of 763 patients with Crohn's disease (CD, 189 diagnosed at age < 19 years), 843 with ulcerative colitis (UC, 179 diagnosed < 19 years), 749 healthy controls, and 546 healthy parents (273 trios) were included in the study.The rs2241880 [autophagy-related 16-like 1 (ATG16L1 )], rs11209026 and rs7517847 [interleukin 23 receptor (IL23R )], rs2066844, rs2066845, rs2066847 (CARD15 ), rs1050152 (OCTN1 ), and rs2631367 (OCTN2 ) gene variants were genotyped. RESULTS:The frequency of G allele of ATG16L1 SNP (Ala197Thr) was increased in patients with CD compared with controls (59% vs 54% respectively) (OR = 1.25, CI = 1.08-1.45,P = 0.003), but not in UC (55%).The frequency of A and G (minor) alleles of Arg381Gln, rs11209026 and rs7517847 variants of IL23R were reduced significantly in CD (4%, OR = 0.62, CI = 0.45-0.87,P = 0.005; 28%, OR = 0.64, CI = 0.55-0.75,P < 0.01), compared with controls (6% and 38%, respectively).The A allele (but not G) was also reduced significantly in UC (4%, OR = 0.69, CI = 0.5-0.94,P = 0.019).No association was demonstrated with sub-phenotypes and interaction with CARD15 , and OCTN1/2 genes, although both gene variants were associated with pediatric-onset disease.CONCLUSION: The present study confirms the association of IL23R polymorphisms with IBD, and ATG16L1 with CD, in both adult-and pediatric-onset subsets in our study population.