Differential transcriptional expresión of the polymorphic myxovirus resistance protein A in response to interferon-alpha treatment.
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.
Fernández-Arcás
Nieves
N
Immunology Service Carlos Haya Hospital, Málaga and Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Málaga, Málaga, Spain.
Blanco
Asunción
A
Gaitán
M Jesús
MJ
Nyqvist
Maria
M
Alonso
Antonio
A
Reyes-Engel
Armando
A
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D019204:GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D016350:Leucine Zippers; D007963:Leukocytes, Mononuclear / Q000502:physiology* / Q000821:virology; D064547:Myxovirus Resistance Proteins; D009975:Orthomyxoviridae / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D000998:Antiviral Agents; D016898:Interferon-alpha; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D012333:RNA, Messenger; D019204:GTP-Binding Proteins