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

Pharmacogenetics. 2004 Mar;14(3):189-93. doi: 10.1097/00008571-200403000-00007.

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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use*
  • GTP-Binding Proteins / genetics*
  • GTP-Binding Proteins / metabolism
  • Humans
  • Interferon-alpha / therapeutic use*
  • Leucine Zippers
  • Leukocytes, Mononuclear / physiology*
  • Leukocytes, Mononuclear / virology
  • Myxovirus Resistance Proteins
  • Orthomyxoviridae / genetics
  • Polymorphism, Single Nucleotide / genetics*
  • Promoter Regions, Genetic / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Transcription, Genetic*

Substances

  • Antiviral Agents
  • Interferon-alpha
  • MX1 protein, human
  • Myxovirus Resistance Proteins
  • RNA, Messenger
  • GTP-Binding Proteins