Polymorphisms in interferon-induced genes and the outcome of hepatitis C virus infection: roles of MxA, OAS-1 and PKR

Interferon stimulates the expression of a number of genes encoding enzymes with antiviral activities, including myxovirus resistance-1 (MxA), 2-5-oligoadenylate synthetase 1 (OAS-1) and double-stranded RNA-dependent protein kinase (PKR). We examined whether polymorphisms in these genes influenced the outcome of hepatitis C virus (HCV) infection. We observed a lower frequency of the GG genotype at position -88 in the MxA gene promoter in self-limiting HCV infection (OR = 0.56; 95% CI: 0.35-0.8; P = 0.010) and in nonresponders to therapy (OR = 0.49; 95% CI: 0.25-0.95; P = 0.020). This genotype predominantly influenced the outcome of treatment in patients with viral genotype 1 (OR = 0.22 95% CI: 0.07-0.67; P = 0.002). A polymorphism in the 3'-untranslated region of the OAS-1 gene was associated with outcome of infection (GG genotype less frequent in self-limiting infection: OR = 0.43; 95% CI: 0.21-0.86; P = 0.010). A polymorphism at position - 168 in the promoter region of the PKR gene was associated with self-limiting infection (CT genotype: OR = 2.75; 95% CI: 1.45-5.24; P = 0.002). Further associations were found with a CGG trinucleotide repeat in the 5' UTR region of the PKR gene. Polymorphisms in the interferon-induced genes, MxA, OAS-1 and PKR appear thus associated with HCV outcome.