title: Investigation of multiple susceptibility loci for inflammatory bowel disease in an Italian cohort of patients.
abstract: 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.
authors.affiliation: Gastroenterology Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy. a.latiano @operapadrepio.it
authors.forename: Anna
authors.initials: A
authors.lastname: Latiano
authors.forename: Orazio
authors.initials: O
authors.lastname: Palmieri
authors.forename: Tiziana
authors.initials: T
authors.lastname: Latiano
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Corritore
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Bossa
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Martino
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Biscaglia
authors.forename: Daniela
authors.initials: D
authors.lastname: Scimeca
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Valvano
authors.forename: Maria
authors.initials: M
authors.lastname: Pastore
authors.forename: Antonio
authors.initials: A
authors.lastname: Marseglia
authors.forename: Renata
authors.initials: R
authors.lastname: D'Incà
authors.forename: Angelo
authors.initials: A
authors.lastname: Andriulli
authors.forename: Vito
authors.initials: V
authors.lastname: Annese
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003093:Colitis, Ulcerative / Q000235:genetics; D003424:Crohn Disease / Q000235:genetics; D003710:Demography; D004843:Epistasis, Genetic; D005260:Female; D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D015212:Inflammatory Bowel Diseases / Q000235:genetics*; D007558:Italy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D055815:Young Adult