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.
Knapp
S
S
Hepatology Section, Faculty of Medicine, Imperial College of Science, Medicine and Technology at St Mary's Hospital, London, UK.
Yee
L J
LJ
Frodsham
A J
AJ
Hennig
B J W
BJ
Hellier
S
S
Zhang
L
L
Wright
M
M
Chiaramonte
M
M
Graves
M
M
Thomas
H C
HC
Hill
A V S
AV
Thursz
M R
MR
D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics*; D020413:3' Untranslated Regions / Q000235:genetics; D020121:5' Untranslated Regions / Q000235:genetics; D000328:Adult; D000998:Antiviral Agents / Q000378:metabolism; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D006526:Hepatitis C / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D064547:Myxovirus Resistance Proteins; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D018911:Trinucleotide Repeats; D019892:eIF-2 Kinase / Q000235:genetics*
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D000998:Antiviral Agents; D016898:Interferon-alpha; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D019892:eIF-2 Kinase; C475085:OAS1 protein, human; D015088:2',5'-Oligoadenylate Synthetase; D019204:GTP-Binding Proteins