Differential transcriptional expresi??n of the polymorphic myxovirus resistance protein A in response to interferon-alpha treatment

Abstract

Levels of myxovirus resistance protein A (MxA) mRNA were studied for a single nucleotide polymorphism in the promoter region at nucleotide position -88 of the gene to identify individual-specific responses to interferon (IFN)-alpha2 that might predict responsiveness to IFN-alpha therapy. We quantified MxA expression by reverse transcription and real-time polymerase chain reaction in peripheral blood mononuclear cells (PBMC) in vitro, induced by IFN-alpha2, from 22 healthy donors, in relation with G/T polymorphism located in the promoter of the MxA. MxA mRNA was significantly upregulated in all subjects (mean of 53-fold) in response to IFN-alpha2 in vitro (P < 0.01). Comparison of the inducibility of MxA mRNA expression in relation with G/T polymorphism showed a 4.26-fold higher induction of MxA mRNA levels in PBMC from carriers of the mutant allele (GT or TT) than homozygotes with the wild-type allele (GG) (P < 0.001). We propose that expression of the IFN-inducible MxA is affected by a single nucleotide polymorphism in the MxA promoter which can identify an individual response to IFN-alpha2.