title: Association of NOD2/CARD15 mutations on Crohn's disease phenotype in an Italian population.
abstract: OBJECTIVE
  To confirm the prevalence of NOD2/CARD15 mutations in Italian inflammatory bowel disease patients and to define the role of the different mutations on Crohn's disease phenotype.
  
  
  METHODS
  A total of 177 patients with Crohn's disease and 92 patients with ulcerative colitis and 164 control participants were investigated for the presence of Arg702Trp, Gly908Arg and Leu1007fsinsC NOD2/CARD15 mutations. Allele frequencies in Crohn's disease and ulcerative colitis patients were compared with those observed in the control population. Genotype-phenotype correlations with the major clinical features were also established and estimated risks (odds ratio with 95% confidence interval) for the mutations were calculated by logistic regression and multiple correspondent analysis.
  
  
  RESULTS
  Gly908Arg and Leu1007fsinsC mutations were significantly more frequent in Crohn's disease patients compared with healthy controls (P<0.01 and <0.003 respectively). Indeed, using a logistic regression model adding terms for age (differently distributed between cases and controls) and sex, a significantly increased risk of having Crohn's disease compared with healthy controls was found for all NOD2 mutations: Leu1007fsinsC (odds ratio=7.35; 95% confidence interval: 1.73-31.3), Gly908Arg (odds ratio=5.70; 95% confidence interval: 1.37-23.7) and Arg702Trp (odds ratio=2.45; 95% confidence interval: 1.10-5.47). As far as the genotype-phenotype correlations are concerned, by multivariate conditional logistic regression methods, we found a significant association between Gly908Arg mutations and familial history of inflammatory bowel disease, between Leu1007fsinsC mutations and appendectomy and between Arg702Trp mutations and fibrostenotic phenotype of Crohn's disease. A nonsignificant association between Arg702Trp variants and ileal disease was also found (odds ratio=8, 95% confidence interval: 0.99-64.9).
  
  
  CONCLUSIONS
  The results of the study confirm a significant association of CARD15 gene mutations in our Italian Crohn's disease population and the impact of different NOD2/CARD15 mutations on specific disease phenotypes.
authors.affiliation: Department of Biology and Genetics for Medical Sciences, University of Milan, Italy.
authors.forename: Vera
authors.initials: V
authors.lastname: Bianchi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Maconi
authors.forename: Sandro
authors.initials: S
authors.lastname: Ardizzone
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Colombo
authors.forename: Elisa
authors.initials: E
authors.lastname: Ferrara
authors.forename: Antonio
authors.initials: A
authors.lastname: Russo
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Tenchini
authors.forename: Gabriele Bianchi
authors.initials: GB
authors.lastname: Porro
mesh_terms: D000328:Adult; D003093:Colitis, Ulcerative / Q000235:genetics; D003424:Crohn Disease / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic
chemical_list: C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein