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CARD8 gene variant is a risk factor for recurrent surgery in patients with Crohn's disease
Adeline Germain1, Rosa-Maria Guéant2, Mathias Chamaillard3
1Department 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.
Insights
Identifying genetic factors for Crohn's disease recurrence is crucial. Caspase recruitment domain-containing protein 8 (CARD8) homozygosity is a novel predictor of repeat surgery, alongside smoking and prior complications.
Area of Science:
- Gastroenterology
- Genetics
- Surgical Outcomes
Background:
- Post-operative recurrence is a significant challenge in Crohn's disease management.
- Genetic factors influencing surgical recurrence are not well understood.
- Risk stratification is needed for targeted therapies to prevent repeat surgeries.
Purpose of the Study:
- To identify genetic variants associated with post-operative surgical recurrence in Crohn's disease.
- To evaluate the role of genetic factors in predicting the need for repeat surgeries.
- To explore potential new markers for risk stratification.
Main Methods:
- Retrospective analysis of Crohn's disease patients with at least one bowel resection from the "Nancy IBD cohort".
- Cox proportional hazard model used for covariate and interaction assessment.
- Kaplan-Meier curves and log-rank tests applied to analyze 200 genetic variants for time to surgical recurrence.
Main Results:
- 28% of 137 patients experienced surgical recurrence.
- Current smoking status, prior post-operative complications, and Caspase recruitment domain-containing protein 8 (CARD8) homozygosity for the risk allele were independently associated with recurrence.
- CARD8 homozygosity showed a significant association (OR 7.56, p=0.036).
Conclusions:
- Current smoking is a significant risk factor for surgical recurrence in Crohn's disease.
- A novel association between CARD8 gene variants and increased risk of surgical recurrence was identified.
- CARD8 may serve as a valuable marker for stratifying patient risk and preventing recurrent surgeries.
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.
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