title: NOD2/CARD15 mutations and presence of granulomas in pediatric and adult Crohn's disease.
abstract: OBJECTIVE
  The etiology and mechanism leading to granuloma formation in patients with Crohn's disease (CD) are presently unknown. The first susceptibility gene to be identified as a risk factor for CD is the NOD2/CARD15 gene on Chromosome 16. Mutations in NOD2 could affect the intracellular response to bacterial products and may eventually lead to granuloma formation. The association between NOD2 and granulomas has not been previously explored. We evaluated a possible association between NOD2 mutations and granuloma formation, and compared the prevalence of granulomas in both pediatric and adult cohorts.
  
  
  METHODS
  Patients were consecutively recruited through pediatric gastroenterology and adult gastroenterology programs. Patients were eligible if CD was confirmed, and they had undergone full colonoscopy with biopsy and/or surgical resection. Patients underwent genotyping for NOD2 disease-associated mutations.
  
  
  RESULTS
  A total of 230 patients were enrolled into the study, of whom 169 patients met all inclusion/exclusion criteria (Group 1, 77 patients [age range 1-16 years]; Group 2, 92 patients [age range 17-68 years]). Surgical resection was performed more often in adults (P < 0.005), and gastroscopy was performed more frequently in children (P < 0.001). Granulomas were found in 34% of the patients studied. The prevalence of granulomas did not differ by age, age group, or gender. A disease-associated NOD2 mutation was found in 37.8% of patients. Granulomas were found in 39% of patients with NOD2 mutations compared with 31% of those without NOD 2 mutations (difference was not significant). In addition, no difference was noted for the specific mutations.
  
  
  CONCLUSIONS
  We did not find any correlation between NOD2 mutations and granuloma formation. The cause of granulomas in CD remains elusive.
authors.affiliation: Bnei Zion Medical Center, Haifa, Israel.
authors.forename: Ron
authors.initials: R
authors.lastname: Shaoul
authors.forename: Amir
authors.initials: A
authors.lastname: Karban
authors.forename: Batia
authors.initials: B
authors.lastname: Weiss
authors.forename: Shimon
authors.initials: S
authors.lastname: Reif
authors.forename: Dror
authors.initials: D
authors.lastname: Wasserman
authors.forename: Avi
authors.initials: A
authors.lastname: Pacht
authors.forename: Rami
authors.initials: R
authors.lastname: Eliakim
authors.forename: Joram
authors.initials: J
authors.lastname: Wardi
authors.forename: Haim
authors.initials: H
authors.lastname: Shirin
authors.forename: Eitan
authors.initials: E
authors.lastname: Wine
authors.forename: Esther
authors.initials: E
authors.lastname: Leshinsky-Silver
authors.forename: Arie
authors.initials: A
authors.lastname: Levine
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003424:Crohn Disease / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D020022:Genetic Predisposition to Disease; D006099:Granuloma / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D006801:Humans; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D007557:Israel / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein; D016133:Polymerase Chain Reaction; D015995:Prevalence; D012307:Risk Factors; D044465:White People
chemical_list: D017931:DNA Primers; D047908:Intracellular Signaling Peptides and Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein