title: Single nucleotide polymorphisms in the interferon-gamma and interleukin-10 genes do not influence chronic hepatitis C severity or T-cell reactivity to hepatitis C virus.
abstract: BACKGROUND
  The mechanisms by which interferon-gamma (IFN-gamma) contributes to inter-individual heterogeneity in the severity of chronic hepatitis C (CH-C) are unknown. In 116 consecutive patients with CH-C, we tested the hypothesis that host genetic factors regulating IFN-gamma production and activity influence the severity of liver damage and hepatitis C virus (HCV)-specific T-cell reactivity.
  
  
  METHODS
  We determined the genotypes of functionally significant polymorphisms in the IFN-gamma gene and in the promoter of interleukin-10 (IL-10), a cytokine that counteracts IFN-gamma. We also measured concanavalin A (Con A)-stimulated IL-10 and IFN-gamma production, and the frequency of virus-specific T-cells, producing IFN-gamma or IL-10.
  
  
  RESULTS
  The grade of inflammation and the stage of fibrosis of CH-C showed no associations with either the IFN-gamma or IL-10 promoter polymorphisms or with Con A-stimulated IL-10 or IFN-gamma production. Similarly, there were no associations between HCV-specific T-cell frequencies and these host genetic factors. On multivariate analysis, the grade of inflammation and the duration of HCV infection accounted for only 37% of the variance in the stage of CH-C (P<0.0001). This percentage did not increase by including any genetic variables in the analyses.
  
  
  CONCLUSIONS
  Future studies investigating the entire cytokine gene sequences will provide better information regarding genetic variations responsible for inter-individual differences in the severity of CH-C.
authors.affiliation: Institute of Hepatology, University College London, 69-75 Chenies Mews, London WC1E 6HX, UK.
authors.forename: William G H
authors.initials: WG
authors.lastname: Abbott
authors.forename: Eirini
authors.initials: E
authors.lastname: Rigopoulou
authors.forename: Philip
authors.initials: P
authors.lastname: Haigh
authors.forename: Helen
authors.initials: H
authors.lastname: Cooksley
authors.forename: Ivana
authors.initials: I
authors.lastname: Mullerova
authors.forename: Marco
authors.initials: M
authors.lastname: Novelli
authors.forename: Alison
authors.initials: A
authors.lastname: Winstanley
authors.forename: Roger
authors.initials: R
authors.lastname: Williams
authors.forename: Nikolai V
authors.initials: NV
authors.lastname: Naoumov
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003208:Concanavalin A / Q000494:pharmacology; D005260:Female; D020022:Genetic Predisposition to Disease; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics* / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology
chemical_list: D003208:Concanavalin A; D016753:Interleukin-10; D007371:Interferon-gamma