CARD8 gene variant is a risk factor for recurrent surgery in patients with Crohn's disease.
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.
['Germain|Adeline|A|', 'Guéant|Rosa-Maria|RM|', 'Chamaillard|Mathias|M|', 'Bresler|Laurent|L|', 'Guéant|Jean-Louis|JL|', 'Peyrin-Biroulet|Laurent|L|']
D000293:Adolescent D000328:Adult D000368:Aged D000369:Aged, 80 and over D000483:Alleles D053468:CARD Signaling Adaptor Proteins D002648:Child D002675:Child, Preschool D015331:Cohort Studies D003092:Colitis D003251:Constriction, Pathologic D003424:Crohn Disease D013505:Digestive System Surgical Procedures D005260:Female D005838:Genotype D006720:Homozygote D006801:Humans D007079:Ileitis D007416:Intestinal Perforation D008297:Male D008875:Middle Aged D015999:Multivariate Analysis D009363:Neoplasm Proteins D020641:Polymorphism, Single Nucleotide D011183:Postoperative Complications D011379:Prognosis D016016:Proportional Hazards Models D012008:Recurrence D012086:Reoperation D012189:Retrospective Studies D012307:Risk Factors D012907:Smoking D055815:Young Adult
CARD8 Crohn's disease Surgical recurrence