CARD15 gene variants and risk of reoperation in Crohn's disease patients

Am J Gastroenterol. 2009 Oct;104(10):2483-91. doi: 10.1038/ajg.2009.413. Epub 2009 Jul 28.


Objectives: Several studies have investigated, with conflicting results, the risk factors for reoperation in Crohn's disease (CD) patients. CARD15 gene variants have been identified as a major genetic risk factor for CD patients and associated with ileal disease, stenosis, and risk of surgery. However, data regarding the association between these variants and the need for reoperation are very few and conflicting. This study evaluated the risk factors of reoperation, including CARD15 gene variants.

Methods: A total of 253 consecutive CD patients, recruited in four Italian tertiary-care inflammatory bowel disease (IBD) referral centers, who had submitted to surgery for CD, were included in the study. Clinical characteristics of CD patients, time and main indications for surgery, type of operation, postoperative therapy, and time to second surgery were recorded. CARD15 gene variants were determined by DNA sequencing analysis in each center. Factors related to surgical recurrence, including CARD15 variants, were estimated by Cox proportional hazard regression.

Results: In all, 89 patients (35.1%) showed at least one surgical recurrence. Reoperation was significantly correlated with stenosis as indications at initial surgery only. CARD15 variants were found in 36.0% of patients, but did not correlate significantly with the demographic and clinical characteristics of the patients, rate of first surgical recurrence, and time to second operation. CARD15 variants did not significantly affect the reoperation rate, irrespective of indications for surgery.

Conclusions: Reoperation for CD is correlated with stenosis at initial surgery, but not with CARD15 gene variants. This finding does not justify more aggressive prophylactic therapy on the basis of CARD15 genotype.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Chi-Square Distribution
  • Crohn Disease / genetics*
  • Crohn Disease / surgery*
  • Female
  • Genetic Variation*
  • Genotype
  • Humans
  • Italy
  • Male
  • Nod2 Signaling Adaptor Protein / genetics*
  • Proportional Hazards Models
  • Recurrence
  • Reoperation
  • Risk Factors
  • Sequence Analysis, DNA


  • NOD2 protein, human
  • Nod2 Signaling Adaptor Protein