Why is the interferon sensitivity-determining region (ISDR) system useful in Japan?
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Updated: Oct 19, 2026

Development and Validation of an Ultrasensitive Single Molecule Array Digital Enzyme-linked Immunosorbent Assay for Human Interferon-α
Published on: June 14, 2018
1Second Department of Internal Medicine, Nagoya University School of Medicine, Japan.
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.