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.
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).


BACKGROUND
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).


CONCLUSIONS
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.
Alvarez-Lobos
Manuel
M
Department of Gastroenterology, Hospital Clínic, Barcelona, Spain.
Arostegui
Juan I
JI
Sans
Miquel
M
Tassies
Dolors
D
Plaza
Susana
S
Delgado
Salvadora
S
Lacy
Antonio M
AM
Pique
Josep M
JM
Yagüe
Jordi
J
Panés
Julián
J
D000328:Adult; D000704:Analysis of Variance; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000032:analysis*; D015331:Cohort Studies; D003082:Colectomy / Q000379:methods; D003424:Crohn Disease / Q000453:epidemiology / Q000235:genetics* / Q000601:surgery*; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020380:Needs Assessment; D053473:Nod2 Signaling Adaptor Protein; D011110:Polymorphism, Genetic; D011183:Postoperative Complications / Q000453:epidemiology; D011237:Predictive Value of Tests; D011336:Probability; D011379:Prognosis; D011446:Prospective Studies; D012008:Recurrence; D012086:Reoperation; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D047908:Intracellular Signaling Peptides and Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein