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). 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.

Carriage of CARD15 variants and smoking as risk factors for resective surgery in patients with Crohn's ileal disease / Laghi, L; Costa, S; Saibeni, S; Bianchi, P; Omodei, P; Carrara, A; Spinas, L; Avesani, Ec; Vecchi, M; De Franchis, R; Malesci, A. - In: ALIMENTARY PHARMACOLOGY & THERAPEUTICS. - ISSN 0269-2813. - 22:6(2005), pp. 557-564. [10.1111/j.1365-2036.2005.02629.x]

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

Laghi L;
2005-01-01

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. 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). 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.
Carriage of CARD15 variants and smoking as risk factors for resective surgery in patients with Crohn's ileal disease / Laghi, L; Costa, S; Saibeni, S; Bianchi, P; Omodei, P; Carrara, A; Spinas, L; Avesani, Ec; Vecchi, M; De Franchis, R; Malesci, A. - In: ALIMENTARY PHARMACOLOGY & THERAPEUTICS. - ISSN 0269-2813. - 22:6(2005), pp. 557-564. [10.1111/j.1365-2036.2005.02629.x]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2876760
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