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Granulomas may be found in 30-70% of patients with Crohn's disease (CD). The etiology of granuloma formation in CD is presently unknown. Elevated levels of TNF-alpha are found within granuloma tissue, and are required to maintain granuloma formation in animal models. TNF-alpha production has been shown to influenced by TNF-alpha promoter polymorphisms. We hypothesized that heterogeneity for granulomas in CD might be influenced by the TNF-alpha promoter genotype. Patients with confirmed CD that had undergone full colonoscopy with multiple biopsies and/or surgical resection, served as the study group. One hundred healthy individuals served as a control population for genotyping. Patients and controls underwent genotyping for four TNF-alpha polymorphisms: 238G/A, 308 G/A,857 C/T, and 863 C/A. Inclusion and exclusion criteria were met in 155 patients (1-68 y). Polymorphisms in the TNF promoter were found in 16.6% (238G/A), 14.5% (308 G/A), 36.6% (857 C/T) and 30.7% (863G/A). No significant association was found for any of the individual polymorphisms with presence or absence of granulomas. In conclusion, we did not find an association between individual polymorphisms in the TNF-alpha promoter and presence of granulomas in CD. The reason for heterogeneity in granuloma formation in patients with CD remains elusive.

Polymorphisms in the TNF-α Promoter and Variability in the Granulomatous Response in Patients with Crohn's Disease