CARD8 gene variant is a risk factor for recurrent surgery in patients with Crohn's disease

Dig Liver Dis. 2015 Nov;47(11):938-42. doi: 10.1016/j.dld.2015.07.013. Epub 2015 Jul 29.

Abstract

Background and aims: Post-operative recurrence is frequent in Crohn's disease. Genetic factors associated with post-operative recurrence remain poorly understood. Identification of genetic variants associated with repeat surgery would allow risk stratification of patients who may benefit from early aggressive therapy and/or post-operative prophylactic treatment.

Methods: Crohn's disease patients who had at least one bowel resection were retrospectively identified from the "Nancy IBD cohort". Covariates and potential interactions were assessed using the Cox proportional hazard model. Kaplan-Meier curves for time to surgical recurrence were developed for 200 genetic variants and analyzed with the log-rank test.

Results: 137 patients had at least 1 resection in our cohort: 38 had a surgical recurrence (28%). In multivariate analysis, current smoker status (OR 6.97, 95% CI 1.85-26.22, p=0.004), post-operative complications after prior surgery (OR 2.72, 95% CI 1.02-7.22, p=0.044), and Caspase recruitment domain-containing protein 8 (CARD8) homozygosity for the risk allele (OR 7.56, 95% CI 1.13-50.37, p=0.036) remained significantly and independently associated with surgical recurrence.

Conclusion: Current smoker status was associated with increased risk of surgical recurrence. A novel association between CARD8 and increased risk of surgical recurrence in Crohn's disease was observed. CARD8 could be a new marker for risk stratification and prevention of recurrent surgery.

Keywords: CARD8; Crohn's disease; Surgical recurrence.

Publication types

  • Observational Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • CARD Signaling Adaptor Proteins / genetics*
  • Child
  • Child, Preschool
  • Cohort Studies
  • Colitis / etiology
  • Colitis / surgery*
  • Constriction, Pathologic / etiology
  • Constriction, Pathologic / surgery
  • Crohn Disease / complications
  • Crohn Disease / genetics
  • Crohn Disease / surgery*
  • Digestive System Surgical Procedures
  • Female
  • Genotype
  • Homozygote
  • Humans
  • Ileitis / etiology
  • Ileitis / surgery*
  • Intestinal Perforation / etiology
  • Intestinal Perforation / surgery*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Proteins / genetics*
  • Polymorphism, Single Nucleotide
  • Postoperative Complications / epidemiology*
  • Prognosis
  • Proportional Hazards Models
  • Recurrence
  • Reoperation / statistics & numerical data
  • Retrospective Studies
  • Risk Factors
  • Smoking / epidemiology*
  • Young Adult

Substances

  • CARD Signaling Adaptor Proteins
  • CARD8 protein, human
  • Neoplasm Proteins