Publikation
Role of the novel Th17 cytokine IL-17F in inflammatory bowel disease (IBD): upregulated colonic IL-17F expression in active Crohn's disease and analysis of the IL17F p.His161Arg polymorphism in IBD
Wissenschaftlicher Artikel/Review - 01.04.2008
Seiderer Julia, Lohse Peter, Müller-Myhsok Bertram, Ochsenkühn Thomas, Göke Burkhard, Konrad Astrid, Schmechel Silke, Jürgens Matthias, Pfennig Simone, Tillack Cornelia, Stallhofer Johannes, Glas Jürgen, Diegelmann Julia, Elben Ira, Brand Stephan
Bereiche
PubMed
DOI
Zitation
Art
Zeitschrift
Veröffentlichungsdatum
ISSN (Druck)
Seiten
Kurzbeschreibung/Zielsetzung
BACKGROUND
Interleukin (IL)-17F, produced in IL-23R-expressing Th17 cells, is a novel member of the IL-17 cytokine family. Given the association of IL23R with inflammatory bowel disease (IBD), we characterized the role of IL-17F in IBD including its intestinal gene expression and the effect of the IL17F p.His161Arg polymorphism on disease susceptibility and phenotype of Crohn's disease (CD) and ulcerative colitis (UC). In addition, we analyzed the IL17F p.His161Arg polymorphism for potential epistasis with IL23R and NOD2/CARD15 variants.
METHODS
Intestinal IL-17F mRNA expression was measured by quantitative polymerase chain reaction (PCR). Genomic DNA from 1682 individuals (CD: n = 499; UC: n = 216; controls: n = 967) was analyzed for the presence of the IL17F p.His161Arg polymorphism, the 3 NOD2 variants, p.Arg702Trp, p.Gly908Arg, and p.Leu1007fsX1008, and 10 CD-associated IL23R variants.
RESULTS
Intestinal IL-17F mRNA expression was 4.4-fold increased in inflamed colonic lesions compared to uninflamed biopsies in CD (P = 0.016) but not in UC. However, the mean intestinal IL-17F mRNA expression was higher in UC than in CD (P < 0.0001). The IL17F p.His161Arg substitution was observed with similar frequencies in IBD patients and controls and was not associated with a certain disease phenotype, but weakly associated with a low body mass index (BMI; P = 0.009) and an earlier age of disease onset (P = 0.039) in UC. There was no evidence for epistasis between the IL17F p.His161Arg polymorphism and IBD-associated single nucleotide polymorphisms within the IL23R gene.
CONCLUSIONS
Intestinal IL17F gene expression is increased in active CD. The IL17F p.His161Arg polymorphism is not associated with IBD susceptibility and has no epistatic interaction with CD-associated IL23R variants.