Why is the interferon sensitivity-determining region (ISDR) system useful in Japan?

J Hepatol. 1999 Jun;30(6):1014-22. doi: 10.1016/s0168-8278(99)80254-2.


Background/aims: The amino acid sequence of NS5A2209-2248, named the "interferon sensitivity-determining region" (ISDR), has been reported to correlate with responsiveness of interferon (IFN) therapy to patients with the hepatitis C virus (HCV) genotype-1b, by several Japanese authors. However, European authors have failed to find this phenomenon, suggesting a difference in HCV-1b isolates between Japan and Europe.

Methods: We compared the HCV-1b nucleotide sequences of our Japanese patients and those of other countries quoted from GenBank, using the envelope 1 sequence.

Results: A phylogenetic tree analysis revealed two characteristic groups from a geographical viewpoint: one group (NJ group) consists of almost entirely non-Japanese isolates, and the other (J group) of almost entirely Japanese isolates. The isolates other than the NJ and J groups are characterized by their specific nucleotide residue, constructing an individual group (W group). Japanese HCV-1b isolates consist of the J group and W group (approximately 40% and 60%, respectively). Comparative study between the two groups in Japanese patients treated with IFN revealed a strong correlation between ISDR type and IFN responsiveness only in the J group, but not in the W group.

Conclusions: These observations convinced us that the existence of the Japan-specific J group is one reason why the ISDR system is useful only in Japan.

Publication types

  • Comparative Study

MeSH terms

  • Base Sequence
  • Europe
  • Hepacivirus / genetics*
  • Hepatitis C, Chronic / therapy*
  • Hepatitis C, Chronic / virology
  • Humans
  • Interferons / therapeutic use*
  • Japan
  • RNA-Dependent RNA Polymerase / analysis*
  • Viral Nonstructural Proteins / analysis*


  • NS-5 protein, hepatitis C virus
  • Viral Nonstructural Proteins
  • Interferons
  • RNA-Dependent RNA Polymerase