Carriage of CARD15 variants and smoking as risk factors for resective surgery in patients with Crohn's ileal disease

L. Laghi, S. Costa, S. Saibeni, P. Bianchi, P. Omodei, A. Carrara, L. Spina, E. Contessini Avesani, M. Vecchi, R. De Franchis, A. Malesci

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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. Aim: 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). Heal resection was the only variable independently associated with CARD 15 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.

Original languageEnglish
Pages (from-to)557-564
Number of pages8
JournalAlimentary Pharmacology and Therapeutics
Issue number6
Publication statusPublished - Sep 15 2005

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)


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