Combined analysis of interferon-γ and interleukin-10 gene polymorphisms and chronic hepatitis C severity

Today there is increasing evidence concerning the contribution of pro-/anti-inflammatory cytokine balance and genetic factors in hepatitis C pathogenesis and interindividual heterogeneity of disease outcome. In the current study, we investigated the influence of functionally described single nucleotide polymorphisms (SNPs) present in interferon-gamma (IFN gamma) and interleukin-10 (IL-10) genes, on chronic hepatitis C severity. IFN gamma (+874T/A) and IL-10 (-10826/A) genotypes were determined in 100 hepatitis C patients with different disease severities (chronic hepatitis, n = 42, liver cirrhosis [LC], and hepatocellular carcinoma in liver cirrhosis [HCC], n = 58) and 103 healthy controls using allele-specific polymerase chain reaction. No statistical differences in allele or genotype distributions of IFNy and IL-10 genes were observed between patients and controls. However, some significant differences in IFNy genotype frequencies were observed between the two groups of patients. IFN gamma(high producer) genotypes TT and TA were significantly more common in patients with LC and HCC (odds ratio = 2.65; p = 0.019). Although IL-10 genotypic frequencies were comparable between the different clinical forms of the disease, the combination of IFN gamma(low producer) and IFN gamma(high producer) genotypes was significantly associated with a lower risk of LC and HCC (odds ratio = 0.21; p = 0.015). In conclusion, our findings suggest that the imbalance between the pro-inflammatory and anti-inflammatory responses mediated by polymorphisms in the IFN gamma and IL-10 genes may influence the outcome of chronic HCV infection. (C) 2009 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.