Knapp S, Yee L J, Frodsham A J, Hennig B J W, Hellier S, Zhang L, Wright M, Chiaramonte M, Graves M, Thomas H C, Hill A V S, Thursz M R
Hepatology Section, Faculty of Medicine, Imperial College of Science, Medicine and Technology at St Mary's Hospital, London, UK.
Genes Immun. 2003 Sep;4(6):411-9. doi: 10.1038/sj.gene.6363984.
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.
干扰素可刺激许多编码具有抗病毒活性的酶的基因表达，包括抗黏液病毒-1（MxA）、2-5-寡腺苷酸合成酶1（OAS-1）和双链RNA依赖性蛋白激酶（PKR）。我们研究了这些基因中的多态性是否会影响丙型肝炎病毒（HCV）感染的结果。我们观察到，在自限性HCV感染中，MxA基因启动子-88位的GG基因型频率较低（比值比=0.56；95%置信区间：0.35-0.8；P=0.010），在治疗无反应者中也是如此（比值比=0.49；95%置信区间：0.25-0.95；P=0.020）。这种基因型主要影响病毒基因型1患者的治疗结果（比值比=0.22，95%置信区间：0.07-0.67；P=0.002）。OAS-1基因3'-非翻译区的多态性与感染结果相关（自限性感染中GG基因型频率较低：比值比=0.43；95%置信区间：0.21-0.86；P=0.010）。PKR基因启动子区-168位的多态性与自限性感染相关（CT基因型：比值比=2.75；95%置信区间：1.45-5.24；P=0.002）。在PKR基因5'UTR区域的CGG三核苷酸重复序列中发现了进一步的关联。因此，干扰素诱导基因MxA、OAS-1和PKR中的多态性似乎与HCV感染结果相关。
