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

Hennig, Branwen J, Frodsham, Angela J, Hellier, Simon, Knapp, Susanne, Yee, Leland J, Wright, Mark, Zhang, Lyna, Thomas, Howard C, Thursz, Mark and Hill, Adrian V (2007) Influence of IL-10RA and IL-22 polymorphisms on outcome of hepatitis C virus infection. Liver International, 27 (8), 1134-43. (doi:10.1111/j.1478-3231.2007.01518.x).

Abstract

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.

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