Influence of IL-10RA and IL-22 polymorphisms on outcome of hepatitis C virus infection.

Background: Two receptor chains, IL-10RA and IL-10RB, are known to mediate the functions of interleukin-10 (IL-10), which has been shown to be involved in the progression of persistent hepatitis C virus (HCV) infection. Little information is available on the role of host genetic variation in IL-10 receptor genes and outcome of HCV infection. IL-22, an IL-10 homologue, shares the IL-10RB receptor chain with IL-10 and has antiviral properties. We investigated the possible role of polymorphisms in the IL-10RA and IL-22 genes in hepatitis C disease pathogenesis. Methods: This study population consisted of 631 HCV patients, recruited from several hepatology clinics across Europe. We genotyped four singlenucleotide polymorphisms (SNPs) in the IL-10RA and six SNPs in the IL-22 gene by ligation detection reaction or restriction fragment length polymorphism. Outcome of HCV infection was assessed according to viral clearance, treatment response, severity of fibrosis and overall inflammation. Conclusions: Variation in IL-10RA appeared to be correlated with response to treatment and inflammation. Two SNPs in IL-22 affected treatment response and viral clearance respectively. We furthermore report on allele and haplotype frequencies and linkage disequilibrium for IL-10RA and IL-22. Our results indicate that genetic variation in these genes may play a modulatory role in the outcome of hepatitis C infection. The prevalence of Hepatitis C is approximately 3% worldwide and an estimated 80% of individuals infected by the hepatitis C virus (HCV) suffer from persistent infection (1). The rate of disease progression is variable and the determinants of the clinical outcome of the disease long-term remain poorly understood. Multiple factors affect the outcome of infectious diseases, including environmental factors and interactions with both pathogens and host genetic factors. There is an increasing body of evidence for the involvement of polymorphic variation in the outcome of persistent HCV infection, influencing the degree of inflammation, severity of fibrosis and response to interferon (IFN) therapy (2‐6). HCV infection may be treated with IFN-a or in combination with ribavirin, but the response to current treatment is variable. Only approximately 20% of infected individuals spontaneously clear the virus (self-limiting infection), whereas the remaining 80% proceed to persistent HCV infection (7). These patients have varying degrees of hepatic inflammation and fibrosis at presentation. Long-term, up to 30% of carriers develop cirrhosis with annual risks of 1‐6% of developing hepatocellular carcinoma and 2‐5% of dying from liver disease (8). The investigation of host genetic factors should help us gain a better understanding of the possible molecular mechanisms underlying susceptibility and differences in disease outcome of HCV infection.