Role of Interleukin-10 polymorphism in determining the outcome of interferon therapy on Hepatitis C patients infected with genotype 3a

Abstract

Pakistan is a low socio economic country having more than 10 million people infected with hepatitis C Virus (HCV) with a major genotype of 3a (GT 3a). Due to high rate of resistance to standard interferon plus ribavirin therapy, it is highly needed to identify new marker for response prediction to therapy. Interleukin 10 (IL-10) is a key member of cytokine, which regulates Th1/Th2 cytokine balance, a major part of immune system against infection. As IL-10 production varies interindividually based on some functional polymorphism in its promoter region. We studied the impact of functionally important polymorphism (- 1082 G/A, -819 C/T and -592 C/A) on HCV infection susceptibility and on outcomes of standard interferon plus ribavirin therapy. 90 healthy subjects and 140 HCV patients (95 were responder and 45 were non-responder to therapy) were included in this study. Amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) method was used for IL-10 polymorphism genotyping. High IL-10 producing -1082 GG genotype (p= 0.02; OR= 0.4; 95% CI= 0.2-0.8) and GTA haplotype (p=0.03; OR= 0.55; 95% CI= 0.3-1) were significantly higher in HCV patients as compared to healthy subjects. IL-10 -1082 GA genotype (p=0.03; OR= 1.95; 95% CI= 1.1-3.4) showed protective effect against HCV infection while other allelic, genotypic and haplotypic variants were nonsignificant among HCV patients compared with healthy controls. The current data failed to show any significant co relation between IL-10 polymorphism inheritance and therapy response in HCV patients. Our data showed a significant effect of IL-10 promoter gene polymorphisms and HCV infection susceptibility or protection but fail to demonstrate the influence of IL-10 promoter gene polymorphisms on the response to combination therapy in Pakistani chronic hepatitis C patients infected with 3a genotype. The impact of genetic variations in IL-10 polymorphic variants on the response to anti-HCV treatment among different ethnic populations deserves further examination.