Mutations in the NOD2/CARD15 gene in Crohn's disease are associated with ileocecal resection and are a risk factor for reoperation.
BACKGROUND
Mutations within the NOD2/CARD15 gene have recently been shown to be associated with Crohn's disease.


OBJECTIVE
To investigate the clinical impact of the three common NOD2/CARD15 mutations in patients with Crohn's disease.


METHODS
We investigated the prevalence of the three common NOD2/CARD15 mutations (Arg702Trp, Gly908Arg, 3020insC) in 180 patients with Crohn's disease, 70 patients with ulcerative colitis and 97 controls. In patients with Crohn's disease, prevalence of NOD2/CARD15 mutations were correlated to clinical and demographical parameters.


RESULTS
In Crohn's disease patients, 35.6% carried at least one mutant allele of NOD2/CARD15 mutations compared with 14.3% of patients with ulcerative colitis (P = 0.006) and to 15.5% of controls (P = 0.0001). Genotype phenotype analyses revealed that NOD2/CARD15 mutations determined younger age at disease diagnosis (P = 0.03), ileal disease location (P = 0.01) and ileocecal resections (P = 0.0002). Interestingly, reoperation with resection of the anastomosis was significantly more frequent in patients with NOD2/CARD15 mutations (P = 0.01).


CONCLUSIONS
Our investigations support the current hypothesis that NOD2/CARD15 mutations are associated with a phenotype of Crohn's disease with younger age at diagnosis, ileal involvement, ileocecal resections and a high risk of postoperative relapse and reoperation. NOD2/CARD15 mutations might therefore be used to identify high risk patients for relapse prevention strategies.
Büning
C
C
Department of Gastroenterology, Hepatology & Endocrinology, Charité, Campus Mitte, Humboldt University, Schumannstrasse 20/21, 10117 Berlin, Germany. carsten.buening@charite.de
Genschel
J
J
Bühner
S
S
Krüger
S
S
Kling
K
K
Dignass
A
A
Baier
P
P
Bochow
B
B
Ockenga
J
J
Schmidt
H H-J
HH
Lochs
H
H
D000293:Adolescent; D000328:Adult; D002352:Carrier Proteins / Q000235:genetics*; D003424:Crohn Disease / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D053473:Nod2 Signaling Adaptor Protein; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods; D020641:Polymorphism, Single Nucleotide
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein