The Role of CARD15 Mutations and Smoking in the Course of Crohn's Disease in a Mediterranean Area

Ematologia II Ospedale V. Cervello, Palermo, Italy.
The American Journal of Gastroenterology (Impact Factor: 10.76). 04/2008; 103(3):649-55. DOI: 10.1111/j.1572-0241.2007.01589.x
Source: PubMed

ABSTRACT To evaluate the role of CARD15 mutations and smoking in the main events of Crohn's disease (CD).
A total of 182 patients with CD were included in a prospective study in order to evaluate the role of CARD15 mutations and smoking in the main outcomes of disease course: first operation and surgical recurrence. The following variables were evaluated in a univariable and multivariable analysis: age, sex, site of disease, pattern, smoking habit, extraintestinal manifestations, duration of disease, and CARD15 mutation. The Kaplan-Meier method for survival curves and Cox model for multivariable analysis were, respectively, used.
A total of 110 patients were operated on and 32 were reoperated on. The 7-yr cumulative free rate of surgery was 42% (95% CI 34-51%). At multivariate analysis only stricturing and penetrating pattern were predictors of surgery (HR 1.7, 95% CI 1-2.8; HR 3.2, CI 1.8-5.5, respectively). The 7-yr cumulative free rate of reoperation was 75% (95% CI 0.52-0.88). At multivariable analysis in the model with any CARD15 mutation, only smoking habit at diagnosis (HR 3.6, 95% CI 1.4-9.1) was predictive of surgical recurrence. When single mutations were considered in the model smoking (HR 4.2, 95% CI 1.8-10.1) and L1007fs mutation (HR 2.9, 95% CI 1.1-7.3) were predictive of reoperation.
In CD, smoking predicts recurrence after surgery. The role of CARD15 mutations in the clinical course of CD remains undefined.

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    • "In addition to its identification as a susceptibility locus, NOD2/D15 has also been identified in studies examining outcomes of CD. The presence of NOD2/CARD15 has been associated with a more aggressive clinical course involving higher risk of intestinal strictures, earlier need for surgical intervention, and less postoperative disease-free intervals.13,73,74 NOD2/CARD15 was also found to be the most important factor for ileal location and stenosing and penetrating disease.72 "
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