NOD2/CARD15 mutations and presence of granulomas in pediatric and adult Crohn's disease.
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.
Shaoul
Ron
R
Bnei Zion Medical Center, Haifa, Israel.
Karban
Amir
A
Weiss
Batia
B
Reif
Shimon
S
Wasserman
Dror
D
Pacht
Avi
A
Eliakim
Rami
R
Wardi
Joram
J
Shirin
Haim
H
Wine
Eitan
E
Leshinsky-Silver
Esther
E
Levine
Arie
A
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
D017931:DNA Primers; D047908:Intracellular Signaling Peptides and Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein