title: Mutations in ISDR of NS5A gene influence interferon efficacy in Chinese patients with chronic hepatitis C virus genotype 1b infection.
abstract: OBJECTIVE
  The interferon sensitivity determining region (ISDR) in the non-structural 5A protein (NS5A) gene of hepatitis C virus genotype 1b (HCV-1b) has been demonstrated in Japanese patients; however, contradictory data have been reported from other parts of the world, particularly from Europe and the USA. This study investigated whether mutations in the ISDR of NS5A gene influence interferon efficacy in Chinese patients with chronic HCV-1b infection.
  
  
  METHODS
  Forty-five Chinese patients with chronic HCV infection were enrolled in a retrospective study. Of these patients, 20 with HCV-1b infection completed an interferon monotherapy course and 6-month follow-up. The pretreatment mutations in the nucleic acid sequence of NS5A 2209-2248 (ISDR) of HCV-1b were identified by sequencing RT-PCR products followed by comparison with the prototype sequence (HCV-J). Correlation with the clinical efficacy of interferon alpha therapy was then analyzed retrospectively.
  
  
  RESULTS
  The statistical analysis indicated a significant correlation between the mutations in ISDR of HCV-1b and sustained virological response to interferon alpha treatment (P < 0.05), and an association of the mutations in ISDR with the pretreatment serum alanine aminotransferase levels (P < 0.01) in Chinese patients with chronic HCV-1b infection.
  
  
  CONCLUSIONS
  The results support the concept that the response of HCV-1b infected patients towards interferon therapy is influenced by the mutations within the ISDR of NS5A gene.
authors.affiliation: Genetics Research Center, South-East University Medical School, Nanjing, Jiangsu, China.
authors.forename: Chuanlai
authors.initials: C
authors.lastname: Shen
authors.forename: Ting
authors.initials: T
authors.lastname: Hu
authors.forename: Ling
authors.initials: L
authors.lastname: Shen
authors.forename: Lei
authors.initials: L
authors.lastname: Gao
authors.forename: Wei
authors.initials: W
authors.lastname: Xie
authors.forename: Jianqiong
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000627:therapeutic use*; D044466:Asian People / Q000235:genetics*; D005500:Follow-Up Studies; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D018937:Hepatitis C Antibodies / Q000097:blood; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D017361:Viral Nonstructural Proteins / Q000235:genetics* / Q000276:immunology; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000410:Alanine Transaminase; D000998:Antiviral Agents; D018937:Hepatitis C Antibodies; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase