The Influence of Polymorphisms in the MxA Promoter and the elF-2α Regulatory Region 2 on the Natural outcome of HBV Infection

Abstract

Interferon(IFN) stimulates the expression of a number of genes encoding enzymes with antiviral activities, including myxovirus resistance A(MxA) and double-stranded RNA-dependent protein kinase(PKR). PKR is also activated by dsRNA, this leads to the phosphorylation of eukaryotic initiation factor 2a(elF-2α), which halts viral replication. We investigated whether polymorphisms in MxA promoter and elF-2α regulatory region 2(elF-2α reg2) influenced the natural outcome of hepatitis B virus(HBV) infection. A total of 243 patients with chronic HBV infection and 160 patients with self-limited HBV infection were used to genotype and identify this single-nucleotide polymorphism(SNP) by polymerase chain reaction-restriction fragment length polymorphism and sequencing, respectively. The distribution of the genotypes(GG, GT, and TT) at position -88 in the MxA promoter was 52.7%, 44.4%, and 2.9% in patients with chronic HBV infection and 41.3%, 43.1%, and 15.6% in patients with self-limited HBV infection, respectively. The frequencies of the TT genotype at position -88 in the MxA promoter were significantly higher among patients with self-limited HBV infection compared with patients with chronic HBV infection (odds ratio=6.24; 95% CI: 2.63-14.81; P=0.001). However, the polymorphisms both at position -123 in the MxA promoter and in the elF-2α reg2 were not significantly different between the two groups (P>0.05). In conclusion, Polymorphism at position -88G/T in the MxA promoter influences the natural outcomes of HBV infection to some extent. This SNP of MxA promoter may be used as a clinical prognostic marker of HBV infection.