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.

Influences of MxA gene –88 G/T and IFN‐gamma +874 A/T on the natural history of hepatitis B virus infection in an endemic area

“…It significantly affects the induction of MxA mRNA expression. Carriers of GT or TT genotype display a markedly higher induction of MxA mRNA levels than those of GG genotype (Fernandez‐Arcas et al ., 2004). In this study, MxA –88 G/T was associated with the natural history of HBV infection with the TT genotype or T allele favourable for the recovery of HBV infection, and the GG genotype or G allele predominant in patients with persistent HBV infection.…”

Polymorphisms of interferon-inducible genes OAS-1 and MxA associated with SARS in the Vietnamese population

“…GG genotype was found more frequently in non-responders of IFN treatment in hepatitis C, and a luciferase reporter assay revealed that the MxA promoter sequence of G haplotype had lower promoter activity than that of T haplotype [31]. Recently, Arcas et al [32] reported that GG genotype expressed lower amount of MxA mRNA than GT or TT genotype in IFN-treated peripheral blood mononuclear cells in vitro. Spiegel et al [15] reported that SARS-CoV replication was not affected in Vero E6 cells that were stably expressing MxA.…”

Single nucleotide polymorphisms and functional analysis of MxA promoter region in multiple sclerosis

“…In case in whom peripheral immune cells express a higher level of MxA, MxA may induce amelioration of MS by enhancing the apoptosis of these immune cells. Recently, Gniadek et al [11] described a study of enhanced apoptosis of peripheral immune cells by IFN-β therapy, and Fernandez-Arcas et al [12] showed higher induction of MxA mRNA by IFN-α 2 in peripheral blood mononuclear cells in patients with − 88T allele than in those with − 88G allele. These interesting studies support the above hypothesis.…”