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Background  Recent GWAs and meta-analyses have outlined about 100 susceptibility genes/loci for inflammatory bowel diseases (IBD). In this study we aimed to investigate the influence of SNPs tagging the genes/loci  PTGER4 ,  TNFSF15 ,  NKX2-3 ,  ZNF365 ,  IFNG ,  PTPN2 ,  PSMG1 , and  HLA  in a large pediatric- and adult-onset IBD Italian cohort.    Methods  Eight SNPs were assessed in 1,070 Crohn's disease (CD), 1,213 ulcerative colitis (UC), 557 of whom being diagnosed at the age of ≤16 years, and 789 healthy controls. Correlations with sub-phenotypes and major variants of  NOD2  gene were investigated.    Results  The SNPs tagging the  TNFSF15 ,  NKX2-3 ,  ZNF365 , and  PTPN2  genes were associated with CD ( P  values ranging from 0.037 to 7×10 −6 ). The SNPs tagging the  PTGER4 ,  NKX2-3 ,  ZNF365 ,  IFNG, PSMG1 , and  HLA  area were associated with UC ( P  values 0.047 to 4×10 −5 ). In the pediatric cohort the associations of  TNFSF15, NKX2-3  with CD, and  PTGER4, NKX2-3, ZNF365, IFNG, PSMG1  with UC, were confirmed. Association with  TNFSF15  and pediatric UC was also reported. A correlation with  NKX2-3  and need for surgery ( P   =  0.038), and with  HLA  and steroid-responsiveness ( P   =  0.024) in UC patients was observed. Moreover, significant association in our CD cohort with  TNFSF15  SNP and colonic involvement (P  =  0.021), and with  ZNF365  and ileal location ( P   =  0.024) was demonstrated.    Conclusions  We confirmed in a large Italian cohort the associations with CD and UC of newly identified genes, both in adult and pediatric cohort of patients, with some influence on sub-phenotypes.

Investigation of Multiple Susceptibility Loci for Inflammatory Bowel Disease in an Italian Cohort of Patients