title: TNF-857 polymorphism in Israeli Jewish patients with inflammatory bowel disease.
abstract: Tumour necrosis factor (TNF)-alpha is an important pro-inflammatory cytokine that has been implicated in the pathogenesis of inflammatory bowel disease (IBD). The promoter TNF-857 C-->T single nucleotide polymorphism (SNP) is functional through the binding to the transcription factor octamer transcription factor-1 (OCT-1). In order to investigate the frequency of this SNP in Israeli Jewish IBD patients, we analysed a cohort of well-characterized patients, 153 with Crohn's disease (CD) and 78 with ulcerative colitis (UC) and 188 healthy controls individually matched for age, sex and ethnicity. Forty-one per cent of the patients were of Ashkenazi and 48% were of non-Ashkenazi background. The remaining 11% were of mixed Ashkenazi-non-Ashkenazi background. Patients and controls were genotyped for the TNF-857 SNP by Taqman technology. Stratification for the CARD15 Arg702Trp, Gly908Arg and Leu1007fsinsC mutations took place in 136 CD patients. Carrier frequency of TNF-857T between CD and controls (36% vs. 40%; P = 0.556; OR: 1.18, 95% CI 0.74-1.88), or between UC and controls (41% vs. 37%; P = 0.743; OR: 0.85, 95% CI 0.45-1.62) did not differ significantly. Neither did stratifying for the presence of at least one of the common CARD15 mutations result in a significant difference between CD and controls. No associations were found between TNF-857T and CD phenotype as defined by the Vienna classification, perianal disease or extra-intestinal disease irrespective of CARD15 carrier status. In conclusion, it appears that TNF-857 SNP does not contribute to susceptibility of IBD, neither does it define the phenotype of CD in Israeli Jewish IBD patients.
authors.affiliation: Department of Gastroenterology, Chaim Sheba Medical Center, 52621 Tel Hashomer, Israel. hermafidder@hotmail.com
authors.forename: Herma H
authors.initials: HH
authors.lastname: Fidder
authors.forename: Roel
authors.initials: R
authors.lastname: Heijmans
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Chowers
authors.forename: Simon
authors.initials: S
authors.lastname: Bar-Meir
authors.forename: Benjamin
authors.initials: B
authors.lastname: Avidan
authors.forename: A Salvador
authors.initials: AS
authors.lastname: Pena
authors.forename: J Bart A
authors.initials: JB
authors.lastname: Crusius
mesh_terms: D000328:Adult; D000483:Alleles; D003093:Colitis, Ulcerative / Q000208:ethnology / Q000235:genetics; D003424:Crohn Disease / Q000208:ethnology / Q000235:genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000208:ethnology / Q000235:genetics*; D007557:Israel; D007585:Jews / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D014409:Tumor Necrosis Factor-alpha