The Role of CARD15 Mutations and Smoking in the Course of Crohn's Disease in a Mediterranean Area
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.
- SourceAvailable from: R. William Depaolo
[Show abstract] [Hide abstract]
- "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 "
ABSTRACT: Crohn's disease is an immune-related disorder characterized by inflammation of the gastrointestinal mucosa, which can occur in any area throughout the digestive tract. This life-long disease commonly presents with abdominal pain, diarrhea, vomiting, and weight loss. While the exact etiology of this disease is largely unknown, it is thought to arise from an interaction between microbial, immunological, and environmental factors in a genetically susceptible host, whereby the immune system attacks the intestine as it cross reacts against gut microbial antigens. The study of genetic variants associated with Crohn's disease has shed light on our understanding of disease pathophysiology. A large number of genetic variants identified in Crohn's disease are related to genes targeting microbial recognition and bacterial wall sensing, the most common being NOD2/CARD15 gene. This review will discuss the recent advance in our knowledge of genetic variants of this disease and how they influence the disease course and prognosis.The Application of Clinical Genetics 07/2013; 6:25-32. DOI:10.2147/TACG.S33966
- [Show abstract] [Hide abstract]
ABSTRACT: The majority of patients with Crohn’s disease require surgery for disease-related complications. Postoperative Crohn’s disease recurrence is common after intestinal resection. The optimal management strategy for postoperative recurrence of Crohn’s disease is controversial. In the absence of universally adopted guidelines, clinicians and patients must discuss and weigh the risks and benefits of postoperative pharmacotherapy. Those patients at low risk of disease recurrence may not require treatment. On the other hand, patients with more aggressive disease and high risk of recurrence may be best treated early in the postoperative period with an immunomodulator or antitumor necrosis factor agents. Ideally, postoperative treatment decisions would be made using predictable, reliable, and reproducible clinical prediction criteria that would guide treatment. This article reviews the data on postoperative Crohn’s disease, including predictors of early recurrence, available options for postoperative monitoring, timing of initiation, and choice of postoperative therapy for prevention and management.
- Inflammatory Bowel Diseases 01/2008; 14(9):1313. DOI:10.1002/ibd.20424 · 4.46 Impact Factor