title: Interferon regulatory factor-1 promoter polymorphism and the outcome of hepatitis C virus infection.
abstract: OBJECTIVE
  Interferon-alpha (IFN-alpha), an important mediator for the host's innate antiviral defense system, has been approved for the treatment of persistent viral infections. We investigated whether two functional polymorphisms in genes involved in IFN-alpha signaling and effector functions are associated with the natural outcome of hepatitis C virus (HCV) infection and the responsiveness of chronic hepatitis C patients to IFN-alpha therapy.
  
  
  METHODS
  Forty-four individuals who had resolved HCV infection spontaneously and 147 patients who developed chronic hepatitis C were analyzed for functional single nucleotide polymorphisms in the promoter regions of the interferon regulatory factor-1 (IRF-1) and myxovirus resistance protein-1 (MxA) genes at positions -300 and -88, respectively.
  
  
  RESULTS
  With regard to -300 IRF-1 or -88 MxA genotype distributions or minor allele frequencies, individuals who spontaneously resolved the infection displayed no significant difference compared with those with chronic infections. Among patients with chronic infections, however, the -300AA IRF-1 genotype, associated with a higher IRF-1 transcriptional activity, was absent in patients with chronic HCV genotype 3a infections, with one exception. In contrast to expectations, -300AA IRF-1 individuals with HCV genotype 3a infection were not represented in higher numbers among those with self-limited infections. Regarding IFN-alpha therapy, -300AA IRF-1 chronic hepatitis C genotype 1 patients tend to respond more often than those with the other IRF-1 genotypes.
  
  
  CONCLUSIONS
  Our findings suggest the possibility that the -300AA IRF-1 genotype is associated with outcome in patients with HCV genotype 3 infection. In addition, in HCV genotype-1-infected patients, this genotype appears associated with response to therapy.
authors.affiliation: Division of Gastroenterology and Endocrinology, Georg-August-Universität, Göttingen, Germany.
authors.forename: Perdita
authors.initials: P
authors.lastname: Wietzke-Braun
authors.forename: Adil B
authors.initials: AB
authors.lastname: Maouzi
authors.forename: Larissa B
authors.initials: LB
authors.lastname: Mänhardt
authors.forename: Heike
authors.initials: H
authors.lastname: Bickeböller
authors.forename: Giuliano
authors.initials: G
authors.lastname: Ramadori
authors.forename: Sabine
authors.initials: S
authors.lastname: Mihm
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics*; D006526:Hepatitis C / Q000188:drug therapy / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000235:genetics*; D016898:Interferon-alpha / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D064547:Myxovirus Resistance Proteins; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012075:Remission, Spontaneous
chemical_list: D000998:Antiviral Agents; D050856:Interferon Regulatory Factor-1; D016898:Interferon-alpha; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D019204:GTP-Binding Proteins