title: Single nucleotide polymorphisms and functional analysis of MxA promoter region in multiple sclerosis.
abstract: OBJECTIVE
  Interferons (IFNs)-inducible myxovirus resistance protein A (MxA) has recently been used as an indirect marker of neutralizing antibody against IFN in patients with multiple sclerosis (MS). On the other hand, MxA inhibits the replication of viruses by means of modifying cellular function, including apoptotic pathway. Our objective is to investigate the genetic and pathological role of MxA in patients with MS.
  
  
  METHODS
  We examined SNPs of MxA promoter region in 67 patients with MS. Moreover, to elucidate the functional roles of SNPs, we conducted Luciferase assay with pGL3-basic vector including patient-derived or artificially mutated MxA promoter region.
  
  
  RESULTS
  A significantly higher frequency of the haplotype with -88T and -123A, which correlates with over-expression of MxA, was observed in MS. Moreover, we elucidated novel findings showing that nt -88 played a leading part with type I IFNs and that nt -123 played the same role independently without type I IFNs, respectively.
  
  
  CONCLUSIONS
  SNPs on MxA promoter region may play an important role in the pathophysiology of MS and provide a novel strategy for the therapeutic resolutions of MS.
authors.affiliation: Department of Neurology, School of Medicine, Sapporo Medical University, Minami 1-jo Nishi 16-chome, Sapporo 060-8543, Japan. furuyama@sapmed.ac.jp
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Furuyama
authors.forename: Susumu
authors.initials: S
authors.lastname: Chiba
authors.forename: Tamaki
authors.initials: T
authors.lastname: Okabayashi
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Yokota
authors.forename: Michio
authors.initials: M
authors.lastname: Nonaka
authors.forename: Tomihiro
authors.initials: T
authors.lastname: Imai
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Fujii
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Matsumoto
mesh_terms: D000328:Adult; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D005786:Gene Expression Regulation; D005787:Gene Frequency; D017930:Genes, Reporter; D006239:Haplotypes / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D007370:Interferon Type I / Q000502:physiology; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics*; D064547:Myxovirus Resistance Proteins; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000032:analysis / Q000096:biosynthesis
chemical_list: D007370:Interferon Type I; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D011993:Recombinant Fusion Proteins; D008156:Luciferases; D019204:GTP-Binding Proteins