Granulomas in Crohn's disease: are newly discovered genetic variants involved?
ABSTRACT 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.
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.
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.
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).
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.
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ABSTRACT: The discovery of a series of genetic and serological markers associated with disease susceptibility and phenotype in inflammatory bowel disease has led to the prospect of an integrated classification system involving clinical, serological and genetic parameters. The Working Party has reviewed current clinical classification systems in Crohn's disease, ulcerative colitis and indeterminate colitis, and provided recommendations for clinical classification in practice. Progress with respect to integrating serological and genetic markers has been examined in detail, and the implications are discussed. While an integrated system is not proposed for clinical use at present, the introduction of a widely acceptable clinical subclassification is strongly advocated, which would allow detailed correlations among serotype, genotype and clinical phenotype to be examined and confirmed in independent cohorts of patients and, thereby, provide a vital foundation for future work.Canadian journal of gastroenterology = Journal canadien de gastroenterologie 10/2005; 19 Suppl A:5-36. · 1.53 Impact Factor
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ABSTRACT: Sigmoidoscopy with a spray of 0.1% indigocarmine was performed on 20 patients with Crohn's disease whose main lesions were located proximal to the transverse colon and on 10 age-matched healthy volunteers. Minute lesions such as apthoid lesions, areas of erythema, and small ulcers were found in 90% of patients with Crohn's disease and in 0% of healthy volunteers (p less than 0.001). Among the minute lesions, aphthoid lesions were found in the highest incidence (85%). It was difficult to determine the presence of aphthoid lesions without the spray of indigocarmine, which facilitated detection. Histologically, granulomas were found in 15% of patients with Crohn's disease. Aphthoid lesions were not associated with superficial erosions and lymphoid follicles. The presence of aphthoid lesions in the rectum and sigmoid colon would be a strong indication of the presence of Crohn's disease.Gastrointestinal Endoscopy 01/1991; 37(3):319-24. · 5.21 Impact Factor
- New England Journal of Medicine 05/2009; 360(17):1785-6. · 51.66 Impact Factor