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.
Conclusion: 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.
Copyright Blackwell Munksgaard 2004