The role of the selenoprotein S (SELS) gene -105G>A promoter polymorphism in inflammatory bowel disease and regulation of SELS gene expression in intestinal inflammation

J. Seiderer, J. Dambacher, B. Kühnlein, S. Pfennig, A. Konrad, H. P. Török, D. Haller, B. Göke, T. Ochsenkühn, P. Lohse, S. Brand

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36 Scopus citations

Abstract

Recently, a -105G>A promoter polymorphism coding for selenoprotein S (SELS) has been shown to increase proinflammatory cytokine expression. We, therefore, analyzed SELS expression and potential phenotypic consequences of the -105G>A polymorphism in patients with inflammatory bowel disease (IBD). SELS mRNA was measured by quantitative polymerase chain reaction (PCR) in intestinal epithelial cells (IEC) after stimulation with proinflammatory cytokines and in human colonic biopsies of IBD patients as well as in murine models of ileitis and murine cytomegalovirus (MCMV) colitis. Genomic DNA from 563 individuals (Crohn's disease: n = 205; ulcerative colitis: n = 154; controls: n = 204) was analyzed for the presence of the SELS -105G>A polymorphism and the three nucleotide-binding oligomerization domain-containing protein 2 (NOD2)/caspase recruitment domain-containing protein 15 (CARD15) variants p.Arg702Trp, p.Gly908Arg and p.Leu1007fsX1008. SELS mRNA expression was increased in IEC after stimulation with proinflammatory cytokines, while its expression was not significantly altered in murine ileitis and MCMV colitis and in inflamed ileal and colonic lesions in IBD patients compared with normal controls. The SELS -105G>A polymorphism was observed with similar frequencies in IBD patients and controls and was not associated with a certain disease phenotype or serum tumor necrosis factor α (TNF-α) levels in these patients. Medium serum TNF-α was 1.27 pg/ml in IBD patients, while none of the controls had TNF-α concentrations above the detection threshold (P < 0.0001). SELS mRNA expression is upregulated by proinflammatory cytokines in IECs but the SELS -105G>A polymorphism is not associated with IBD susceptibility and does not contribute to a certain disease phenotype or increased TNF-α levels in IBD patients.

Original languageEnglish
Pages (from-to)238-246
Number of pages9
JournalTissue Antigens
Volume70
Issue number3
DOIs
StatePublished - Sep 2007

Keywords

  • Inflammatory bowel disease
  • Intestinal inflammation
  • Polymorphism
  • Selenoprotein S

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