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Gastroenterology and Hepatology - Pediatrics and Child Health


Investigation of Multiple Susceptibility Loci for Inflammatory Bowel Disease in an Italian Cohort of Patients
Published: Wednesday, July 27, 2011
Author: Anna Latiano et al.

by Anna Latiano, Orazio Palmieri, Tiziana Latiano, Giuseppe Corritore, Fabrizio Bossa, Giuseppina Martino, Giuseppe Biscaglia, Daniela Scimeca, Maria Rosa Valvano, Maria Pastore, Antonio Marseglia, Renata D'Incà, Angelo Andriulli, Vito Annese

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.

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