Interleukin-10 promoter polymorphisms and the outcome of hepatitis C virus infection.
The natural outcome and response to treatment in hepatitis C virus (HCV) infection varies between individuals. Whereas some variation may be attributable to viral and environmental variables, it is probable that host genetic background also plays a significant role. Interleukin (IL)-10 has a key function in the regulation of cellular immune responses and in the suppression of pro-inflammatory cytokine secretion. Functional polymorphisms in the IL-10 gene have been described. We investigated the role of these polymorphisms in the outcome of HCV infection, treatment response and development of fibrosis in a case-control association study. Self-limiting infection was associated with the IL-10 (-592) AA genotype (OR=2.05; P=0.028). Persistent infection was associated with the IL-10 (-1082) GG genotype (OR=0.48; P=0.018). Sustained response to interferon therapy was associated with the IL-10 (-1082) GG genotype (OR=2.28; P=0.005) and the haplotype GCC (OR=2.27; P=0.020). The IL-10 (-1082) AA genotype and the ATA/ATA and ACC/ACC homozygous haplotypes were more frequent among patients with rapid fibrosis. Furthermore, the microsatellites IL-10.R and IL-10.G were associated with interferon response with IL-10R.2 conveying susceptibility (OR=1.80; P=0.034), and IL-10R.3 and IL-10.G13 being protective (OR=0.47; P=0.003 and OR=0.59; P=0.042, respectively). We conclude that polymorphisms in the IL-10 promoter appear to have some influence on the outcome of HCV infection, treatment and development of fibrosis.
Knapp
Susanne
S
Faculty of Medicine, Imperial College, St Mary's Hospital Campus, Norfolk Place, W2 1NY, London, UK.
Hennig
Branwen J W
BJ
Frodsham
Angela J
AJ
Zhang
Lyna
L
Hellier
Simon
S
Wright
Mark
M
Goldin
Rob
R
Hill
Adrian V S
AV
Thomas
Howard C
HC
Thursz
Mark R
MR
D018450:Disease Progression; D005260:Female; D005355:Fibrosis; D006239:Haplotypes; D006526:Hepatitis C / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D016896:Treatment Outcome
D016753:Interleukin-10