title: Mutations in the NOD2/CARD15 gene in Crohn's disease are associated with ileocecal resection and are a risk factor for reoperation.
abstract: 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.
authors.affiliation: Department of Gastroenterology, Hepatology & Endocrinology, Charité, Campus Mitte, Humboldt University, Schumannstrasse 20/21, 10117 Berlin, Germany. carsten.buening@charite.de
authors.forename: C
authors.initials: C
authors.lastname: Büning
authors.forename: J
authors.initials: J
authors.lastname: Genschel
authors.forename: S
authors.initials: S
authors.lastname: Bühner
authors.forename: S
authors.initials: S
authors.lastname: Krüger
authors.forename: K
authors.initials: K
authors.lastname: Kling
authors.forename: A
authors.initials: A
authors.lastname: Dignass
authors.forename: P
authors.initials: P
authors.lastname: Baier
authors.forename: B
authors.initials: B
authors.lastname: Bochow
authors.forename: J
authors.initials: J
authors.lastname: Ockenga
authors.forename: H H-J
authors.initials: HH
authors.lastname: Schmidt
authors.forename: H
authors.initials: H
authors.lastname: Lochs
mesh_terms: 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
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein