title: Carriage of CARD15 variants and smoking as risk factors for resective surgery in patients with Crohn's ileal disease.
abstract: BACKGROUND
  It is controversial whether CARD15 variants are truly associated with a more severe form of Crohn's disease. The relative role of CARD15 genotype and smoking in Crohn's disease progression is also debated.
  
  
  OBJECTIVE
  To investigate the association between CARD15 variants and history of resective surgery in patients with Crohn's ileal disease, taking into account smoking as a possible confounding factor.
  
  
  METHODS
  We originally assessed CARD15 genotype in 239 north Italian Crohn's disease patients (mean follow-up: 10.1 +/- 8.1 years). We then focused on 193 patients with proven ileal involvement, 70 of whom (36.3%) carried CARD15-mutated alleles (G908R, R702W, L1007fs).
  
  
  RESULTS
  Carriage of CARD15 variants was positively associated with family history and ileal-only disease and negatively associated with uncomplicated behaviour at maximal follow-up (P < 0.05). Ileal resection was the only variable independently associated with CARD15 variants at multivariate analysis (OR 3.8; 95% CI 1.6-9.2; P = 0.003). Kaplan-Meier analysis showed that ileal resection was favoured both by CARD15 variant-carriage (P = 0.01) and by smoking (P = 0.05), but smoking did not affect progression to surgery in variant carriers (P = 0.31). Thirteen of 14 (93%) patients being resection-free at 15-year follow-up, had CARD15 wild-type genotype (P = 0.01), whereas only seven (50%) had never smoked (P = 1.0).
  
  
  CONCLUSIONS
  In summary, CARD15 variant-associated Crohn's ileitis is virtually committed to stricturing and/or penetrating disease and, eventually, to resective surgery. Smoking accelerates progression to surgery in patients with wild-type CARD15 genotype, but it seems to exert no additional effect in CARD15-variant carriers.
authors.affiliation: Division of Gastroenterology, Istituto Clinico Humanitas, Rozzano, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Laghi
authors.forename: S
authors.initials: S
authors.lastname: Costa
authors.forename: S
authors.initials: S
authors.lastname: Saibeni
authors.forename: P
authors.initials: P
authors.lastname: Bianchi
authors.forename: P
authors.initials: P
authors.lastname: Omodei
authors.forename: A
authors.initials: A
authors.lastname: Carrara
authors.forename: L
authors.initials: L
authors.lastname: Spina
authors.forename: E
authors.initials: E
authors.lastname: Contessini Avesani
authors.forename: M
authors.initials: M
authors.lastname: Vecchi
authors.forename: R
authors.initials: R
authors.lastname: De Franchis
authors.forename: A
authors.initials: A
authors.lastname: Malesci
mesh_terms: D000328:Adult; D003424:Crohn Disease / Q000235:genetics* / Q000601:surgery; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007077:Ileal Diseases / Q000235:genetics* / Q000601:surgery; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D053473:Nod2 Signaling Adaptor Protein; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein