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

• Published in: Liver international 2007-10, Vol.27 (8), p.1134-1143
• Main Authors: Hennig, Branwen J., Frodsham, Angela J., Hellier, Simon, Knapp, Susanne, Yee, Leland J., Wright, Mark, Zhang, Lyna, Thomas, Howard C., Thursz, Mark, Hill, Adrian V.
• Format: Article
• Language: English
• Subjects: Adult; Antiviral Agents - therapeutic use; Case-Control Studies; case-control study; DNA Mutational Analysis; Europe; Female; Gene Frequency; Haplotypes; hepatitis C; Hepatitis C - drug therapy; Hepatitis C - genetics; Hepatitis C virus; Humans; IL-10RA; IL-22; Interleukin-10 Receptor alpha Subunit - genetics; Interleukin-22; Interleukins - genetics; Linkage Disequilibrium; Male; polymorphism; Polymorphism, Single Nucleotide; Treatment Outcome
• ISSN: 1478-3223; 1478-3231; 1399-1698
• DOI: 10.1111/j.1478-3231.2007.01518.x

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 single‐nucleotide 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.