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.
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.
Abbott
William G H
WG
Institute of Hepatology, University College London, 69-75 Chenies Mews, London WC1E 6HX, UK.
Rigopoulou
Eirini
E
Haigh
Philip
P
Cooksley
Helen
H
Mullerova
Ivana
I
Novelli
Marco
M
Winstanley
Alison
A
Williams
Roger
R
Naoumov
Nikolai V
NV
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
D003208:Concanavalin A; D016753:Interleukin-10; D007371:Interferon-gamma