Crohn's disease patients carrying Nod2/CARD15 gene variants have an increased and early need for first surgery due to stricturing disease and higher rate of surgical recurrence

Abstract

Objective: To study the predictive value of Nod2/CARD15 gene variants along with disease phenotypic characteristics for requirement of initial surgery and for surgical recurrence in Crohn's disease (CD).

Summary background data: Nod2/CARD15 gene variants play an important role in the susceptibility to CD. Studies of genotype-phenotype relationship suggest that these variants are associated with development of intestinal strictures. Preliminary reports analyzing the association between these variants and need for surgery have produced inconsistent results.

Methods: A total of 170 CD patients were included prospectively in the study and followed up regularly for a mean of 7.4 +/- 6.1 years. Clinical characteristics of CD, time and indication for surgery, and recurrence were registered. Nod2/CARD15 gene variants were determined by DNA sequencing analysis.

Results: Surgery for stricturing disease was significantly more frequent in patients with Nod2/CARD15 variants in the univariate analysis (odds ratio [OR], 3.63; 95% confidence interval [CI], 1.42-9.27), and it was required at an earlier time (P = 0.004). Only Nod2/CARD15 variants (OR, 3.58; 95% CI, 1.21-10.5) and stricturing phenotype at diagnosis of CD (OR, 9.34; 95% CI, 2.56-33.3) were independent predictive factors of initial surgery for stricturing lesions in the multivariate analysis. Among 70 patients that required surgery, postoperative recurrence was also more frequent in patients with Nod2/CARD15 variants in the univariate and multivariate analysis (OR, 3.29; 95% CI, 1.13-9.56), and reoperation was needed at an earlier time (P = 0.03).

Conclusion: Nod2/CARD15 variants are associated with early initial surgery due to stenosis and with surgical recurrence in Crohn's disease. Patients with these variants could benefit from preventive and/or early therapeutic strategies.

FIGURE 1. Actuarial probability of remaining free of surgery according to Nod2/CARD15 gene status.

FIGURE 2. Actuarial probability of remaining free of initial surgery for treatment of stricturing lesions according to Nod2/CARD15 gene status.

FIGURE 3. Actuarial probability of remaining free of surgical recurrence according to Nod2/CARD15 gene status.

FIGURE 4. Actuarial probability of remaining free of surgery for treatment of stricturing lesions during the course of CD according to Nod2/CARD15 gene status.