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Granulomas in Crohn's disease: Are newly discovered genetic variants involved?

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Background: Non-caseating granulomas exist in a substantial portion of patients with Crohn's disease (CD). Several single nucleotide polymorphisms (SNPs) have been identified as a having strong association with CD, including SNPs within the autophagy related 4 homolog A (ATG4A) gene and the neutrophil cytosolic factor 4 (NCF4) gene. We hypothesized a possible association between the presence of granulomas in CD patients and variants in the ATG4A and NCF4 genes. Aims: To investigate whether variants in the NCF4 and ATG4A genes are associated with granuloma formation in a cohort of Israeli patients with CD, exploring demographic and clinical characteristics that differ between granuloma positive and granuloma negative patients. Methods: 307 Israeli patients with CD were studied. Patients with CD who underwent biopsy or resection of the intestine were classified according to presence or absence of granulomas. Using PCR-RFLP we determined the allele frequency in SNP rs4821544 (NCF4 gene) and SNP rs807185 (ATG4A gene) for all patients. Results: Granulomas were found in 85 out of 307 CD patients (27%). There were no significant differences between patients with or without granulomas in allele frequency in SNPs rs4821544 and rs807185. CD Patients with granuloma were younger at diagnosis than patients without granuloma (mean age 19 vs. 27, respectively, P<0.0001) and were more likely to undergo surgery (55.3% vs. 34.8%, respectively, P=0.002). Conclusions: No association was found between SNPs rs4821544 and rs807185 and the presence of granulomas in CD patients. Granuloma positive patients were more likely to be younger and to undergo surgery. © 2010 Elsevier B.V.




Mazor, Y., Karban, A., Nesher, S., Weiss, B., Leshinsky-Silver, E., Levine, A., & Eliakim, R. (2010). Granulomas in Crohn’s disease: Are newly discovered genetic variants involved? Journal of Crohn’s and Colitis, 4(4), 438–443.

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