title: Polymorphisms in the TNF-alpha promoter and variability in the granulomatous response in patients with Crohn's disease.
abstract: 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.
authors.affiliation: Department of Pediatrics, E.Wolfson Medical Center, Holon 58100, Isreal.
authors.forename: Ilan
authors.initials: I
authors.lastname: Dalal
authors.forename: Amir
authors.initials: A
authors.lastname: Karban
authors.forename: Eytan
authors.initials: E
authors.lastname: Wine
authors.forename: Rami
authors.initials: R
authors.lastname: Eliakim
authors.forename: Haim
authors.initials: H
authors.lastname: Shirin
authors.forename: Marcelo
authors.initials: M
authors.lastname: Fridlender
authors.forename: Ron
authors.initials: R
authors.lastname: Shaoul
authors.forename: Esther
authors.initials: E
authors.lastname: Leshinsky-Silver
authors.forename: Arie
authors.initials: A
authors.lastname: Levine
mesh_terms: D000328:Adult; D001706:Biopsy; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D003424:Crohn Disease / Q000235:genetics* / Q000473:pathology*; D006099:Granuloma / Q000235:genetics*; D006801:Humans; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D014409:Tumor Necrosis Factor-alpha