NOD2 mutations predict the risk for surgery in pediatric-onset Crohn's disease.
OBJECTIVE
Three common mutations of the NOD2/CARD15 gene have been associated with Crohn disease (CD), ileal disease location, and fibrostenotic behavior. The aim of this study was to investigate the effect of these mutations on disease manifestation and the risk of surgery in a cohort of German childhood-onset CD patients.


METHODS
Genotyping for the NOD2 mutations p.Arg702Trp, p.Gly908Arg, and p.1007fs was performed in 171 CD children (onset of disease <17 years; mean 11.8 years) and in 253 controls. NOD2 mutation status was correlated with the need for surgery during childhood.


RESULTS
Seventy-eight children (45.6%) were carriers of at least 1 NOD2 mutation versus 36 (14.2%) in the control group (P < .0001). NOD2 mutations were highly associated with CD and stricturing behavior (P < .0001), with the p.1007fs mutation also conferring a risk for isolated ileal disease (P = .003). Thirty-two children (18.7%) needed an intestinal resection with a significant association between the need of surgery and NOD2 carrier status. Surgery occurred at an earlier stage of disease in children with p.1007fs mutations.


CONCLUSIONS
In children with pediatric-onset CD, the need for surgical therapy younger than 17 years is associated with the NOD2 genotype. Genetic testing therefore may identify children with CD who are at risk.
Lacher
Martin
M
Department of Pediatric Surgery, Research Laboratories, University of Munich, D-80337 Munich, Germany. martin.lacher@lmu.de
Helmbrecht
Johanna
J
Schroepf
Sebastian
S
Koletzko
Sibylle
S
Ballauff
Antje
A
Classen
Martin
M
Uhlig
Holm
H
Hubertus
Jochen
J
Hartl
Dominik
D
Lohse
Peter
P
von Schweinitz
Dietrich
D
Kappler
Roland
R
D000293:Adolescent; D017668:Age of Onset; D002648:Child; D003424:Crohn Disease / Q000235:genetics* / Q000601:surgery*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007077:Ileal Diseases / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D009154:Mutation / Q000235:genetics*; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D010641:Phenotype; D012307:Risk Factors
D047908:Intracellular Signaling Peptides and Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein