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


CONCLUSIONS
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.
Department of Digestive Surgery, University Hospital of Nancy-Brabois, Vandoeuvre-les-Nancy, France; INSERM U954, Nutrition-Génétique et Exposition aux risques environnementaux, Faculté de Médecine, Université de Lorraine, Vandoeuvre-les-Nancy, France. Electronic address: a.germain@chu-nancy.fr.
Adeline
A
Germain
INSERM U954, Nutrition-Génétique et Exposition aux risques environnementaux, Faculté de Médecine, Université de Lorraine, Vandoeuvre-les-Nancy, France.
Rosa-Maria
RM
Guéant
Institut Pasteur de Lille, Center for infection and immunity of Lille, Lille, France; INSERM U1019, Team 7, Equipe FRM, Lille, France.
Mathias
M
Chamaillard
Department of Digestive Surgery, University Hospital of Nancy-Brabois, Vandoeuvre-les-Nancy, France.
Laurent
L
Bresler
INSERM U954, Nutrition-Génétique et Exposition aux risques environnementaux, Faculté de Médecine, Université de Lorraine, Vandoeuvre-les-Nancy, France.
Jean-Louis
JL
Guéant
INSERM U954, Nutrition-Génétique et Exposition aux risques environnementaux, Faculté de Médecine, Université de Lorraine, Vandoeuvre-les-Nancy, France; Department of Gastroenterology, University Hospital of Nancy-Brabois, Vandoeuvre-les-Nancy, France.
Laurent
L
Peyrin-Biroulet
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003092:Colitis / Q000209:etiology / Q000601:surgery*; D003251:Constriction, Pathologic / Q000209:etiology / Q000601:surgery; D003424:Crohn Disease / Q000150:complications / Q000235:genetics / Q000601:surgery*; D013505:Digestive System Surgical Procedures; D005260:Female; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007079:Ileitis / Q000209:etiology / Q000601:surgery*; D007416:Intestinal Perforation / Q000209:etiology / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011183:Postoperative Complications / Q000453:epidemiology*; D011379:Prognosis; D016016:Proportional Hazards Models; D012008:Recurrence; D012086:Reoperation / Q000706:statistics & numerical data; D012189:Retrospective Studies; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology*; D055815:Young Adult
D053468:CARD Signaling Adaptor Proteins; C455623:CARD8 protein, human; D009363:Neoplasm Proteins
CARD8; Crohn's disease; Surgical recurrence