Investigation of multiple susceptibility loci for inflammatory bowel disease in an Italian cohort of patients

• Published in: PloS one 2011-07, Vol.6 (7), p.e22688-e22688
• Main Authors: Latiano, Anna, Palmieri, Orazio, Latiano, Tiziana, Corritore, Giuseppe, Bossa, Fabrizio, Martino, Giuseppina, Biscaglia, Giuseppe, Scimeca, Daniela, Valvano, Maria Rosa, Pastore, Maria, Marseglia, Antonio, D'Incà, Renata, Andriulli, Angelo, Annese, Vito
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Alleles; Analysis; Biology; Case-Control Studies; Child; Child, Preschool; Chromosomes; Cohort Studies; Colitis, Ulcerative - genetics; Colon; Correlation; Crohn Disease - genetics; Crohn's disease; Demography; Disease susceptibility; Epistasis, Genetic; Female; Genes; Genetic aspects; Genetic Loci - genetics; Genetic Predisposition to Disease; Histocompatibility antigen HLA; Humans; Infant; Inflammatory bowel disease; Inflammatory bowel diseases; Inflammatory Bowel Diseases - genetics; Intestine; Italy; Loci; Male; Marking; Medical research; Medicine; Middle Aged; Multivariate Analysis; Nkx2.3 protein; NOD2 protein; Patients; Pediatrics; Phenotype; Polymorphism, Single Nucleotide - genetics; PTPN2 protein; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Surgery; Tagging; Tumor necrosis factor-TNF; Ulcerative colitis; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0022688

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. 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. 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. 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.