title: Associations between responses to interferon therapy and genetic variation in interleukin-28B and the core region of hepatitis C virus genotype 3a.
abstract: The single-nucleotide polymorphism (SNP) of interleukin-28B (IL-28B) and mutations in the core region of hepatitis C virus (HCV) genotype 1b have been associated with response to interferon (IFN) therapy. However, whether this IL-28B SNP affects responses to INF therapy for HCV genotype 3a is not known. The aim of this study is to investigate whether this IL-28B SNP (rs8099917) and specific missense mutations in the HCV core region affect the response to IFN therapy for HCV genotype 3a. Patients (n = 19; median age 44.5) infected with HCV genotype 3a who received IFN therapy were studied. Of the 19 patients, 12 (63.1%) achieved sustained virological response. Of those 12 patients, 11 had the TT genotype (11/16; 68.7%), and one had the TG genotype (1/3; 33.3%). The difference in the sustained virological response rate between IL-28B genotype groups was not significant (P = 0.5232). HCV core region was well conserved; however, polymorphisms at position 72 were identified. Of the 19 HCV samples; 15 carried a glutamic acid at position 72, and these were defined as E type; the others (4/19) were defined as non-E type. Notably, there was a significant difference in the sustained virological response rate between E type and non-E-type; 12 of the 15 patients with E-type achieved sustained virological response, but none of the four patients with non-E-type achieved sustained virological response (P = 0.009). A glutamic acid at position 72 in the core region of HCV genotype 3a was associated with a good response to IFN therapy. J. Med. Virol. 87:1361-1367, 2015. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Ishigami
authors.affiliation: Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors.forename: Teiji
authors.initials: T
authors.lastname: Kuzuya
authors.affiliation: Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Honda
authors.affiliation: Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Hayashi
authors.affiliation: Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors.forename: Hidemi
authors.initials: H
authors.lastname: Goto
mesh_terms: D000328:Adult; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D016896:Treatment Outcome; D014758:Viral Core Proteins / Q000235:genetics*; D000095022:Interferon Lambda
chemical_list: D007372:Interferons; D007378:Interleukins; D014758:Viral Core Proteins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C069130:nucleocapsid protein, Hepatitis C virus
keywords: amino acid substitution; core region; genotype 3a; sustained virological response