title: Relationship between CARD15, SLC22A4/5, and DLG5 polymorphisms and early-onset inflammatory bowel diseases: an Italian multicentric study.
abstract: BACKGROUND
  Inflammatory bowel disease (IBD) has been associated with several polymorphisms in genes likely involved in innate immune responses and integrity of epithelial mucosal barrier. A major role in adult Crohn's disease (CD) has been defined for 3 polymorphisms in the CARD15 gene, whereas variants in the SLC22A4, SLC22A5, and DLG5 genes could have a minor contribution to IBD susceptibility.
  
  
  METHODS
  We analyzed a panel of 6 polymorphisms within these genes in 227 Italian early-onset IBD patients (134 CD, 93 ulcerative colitis [UC]; age at diagnosis <or=18 years) and 166 unaffected control subjects.
  
  
  RESULTS
  Each CARD15 variant was found to be independently associated with CD. After the genotypes at the 3 polymorphisms were combined, 37.3% patients carried at least 1 variant compared with 9.2% control subjects (odds ratio, 5.87; 95% CI 3.11-11.1; P < 0.001). The combined frequency of CARD15 variants was also higher in UC children compared with control subjects (14% vs 9.2%), but this difference was not significant. However, CARD15 variants were associated with earlier onset of UC, and the mutation rate was significantly higher in UC patients with onset at or before 6 years of age compared with control subjects (27.6% vs 9.2%) (odds ratio = 3.76; 95% CI 1.42-9.94; P = 0.01). CARD15 variants also were associated with ileal CD involvement and a higher rate of extraintestinal manifestations in UC. Allele and genotype frequencies at SLC22A and DLG5 polymorphisms were not significantly different between cases and controls.
  
  
  CONCLUSIONS
  Our results demonstrate that in the Italian population, the major CARD15 polymorphisms are associated with susceptibility to early-onset CD and with ileal involvement and suggest a previously unreported association with very early-onset, severe UC.
authors: IRCCS CSS Hospital, San Giovanni Rotondo, and CSS-Mendel Institute, Rome, Italy.
authors: Alessandro
authors: A
authors: Ferraris
authors: Barbara
authors: B
authors: Torres
authors: Daniela
authors: D
authors: Knafelz
authors: Arrigo
authors: A
authors: Barabino
authors: Paolo
authors: P
authors: Lionetti
authors: Gian Luigi
authors: GL
authors: de Angelis
authors: Giuseppe
authors: G
authors: Iacono
authors: Bronislava
authors: B
authors: Papadatou
authors: Giovanna
authors: G
authors: D'Amato
authors: Vincenzo
authors: V
authors: Di Ciommo
authors: Bruno
authors: B
authors: Dallapiccola
authors: Massimo
authors: M
authors: Castro