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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.

Original publication

DOI

10.1038/sj.gene.6363984

Type

Journal article

Journal

Genes Immun

Publication Date

09/2003

Volume

4

Pages

411 - 419

Keywords

2',5'-Oligoadenylate Synthetase, 3' Untranslated Regions, 5' Untranslated Regions, Adult, Antiviral Agents, Female, GTP-Binding Proteins, Gene Expression Regulation, Genotype, Hepacivirus, Hepatitis C, Humans, Interferon-alpha, Male, Myxovirus Resistance Proteins, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, Trinucleotide Repeats, eIF-2 Kinase