title: Contribution of Irf-1 promoter polymorphisms to the Th1-type cell response and interferon-beta monotherapy for chronic hepatitis C.
abstract: We recently reported promoter polymorphisms in the IRF-1 gene, an interferon-inducible gene that plays an important role in host antiviral function. The promoter activity was shown to be different between different polymorphisms. In this study, we investigated the relationship between IRF-1 promoter polymorphisms and the response to interferon monotherapy for chronic hepatitis C. Eighteen patients with a low initial viral load or hepatitis C virus (HCV) genotype non-1b received 6-months course of interferon-beta monotherapy. IRF-1 gene mutations and the treatment response were investigated. The IRF-1 promoter type possessing a higher promoter activity (-415C/-410A/-300A) was found in only three patients, all of which had a lower viral load than those with other promoter types and were able to obtain a sustained viral response. Flow cytometric analysis of peripheral blood mononuclear cells showed that the patients with a higher promoter activity of the IRF-1 had a significantly higher proportion of T helper 1-type CD4(+) cells after interferon administration than those of other promoter types. These results suggest that IRF-1 promoter polymorphisms may contribute, at least partially, to host antiviral activity for chronic hepatitis C.
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8581, Japan.
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Saito
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Tada
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Nakamoto
authors.forename: Kumi
authors.initials: K
authors.lastname: Kitamura
authors.forename: Hiromi
authors.initials: H
authors.lastname: Horikawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kurita
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Ebinuma
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Ishii
authors.forename: Masahiko
authors.initials: M
authors.lastname: Takahashi
authors.forename: Shin
authors.initials: S
authors.lastname: Tanaka
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Hibi