title: Impact of genetic polymorphisms near the IL28B gene and amino acid substitutions in the hepatitis C virus core region on interferon sensitivity/resistance in patients with chronic hepatitis C.
abstract: It has been reported that genetic polymorphisms near the IL28B gene or amino acid substitutions in hepatitis C virus (HCV) core protein are associated with the clinical outcome of peginterferon (PEG-IFN) and ribavirin combination therapy. The impact of these factors on the pure sensitivity/resistance to interferon was evaluated. Changes in the HCV RNA levels 24, 48, 72, and 120 hr after administering a single dose of standard interferon (IFN) were measured in 156 HCV-infected patients. The changes were compared based on the genetic polymorphisms near the IL28B gene or amino acid substitutions in the HCV core region. Among patients with HCV genotype 1b, there were differences in the reduction and subsequent increase in HCV RNA levels after administering IFN based on rs8099917 genetic polymorphisms. Amino acid substitutions at residue 70 were associated with differences in the changes in HCV RNA levels only in patients with TG/GG genotype. Multivariate analyses showed that genetic polymorphisms near the IL28B gene was the sole independent factor that was associated with the reduction in HCV RNA levels after administering IFN and the final response to the combination therapy. Among patients infected with HCV genotype 2a or 2b, there were no differences in the changes in HCV RNA levels based on the genetic polymorphisms near the IL28B gene. In HCV genotype 1b, genetic variations near the IL28B gene affected the sensitivity/resistance to IFN strongly. Genetic polymorphisms near the IL28B gene did not affect the sensitivity/resistance to IFN in HCV genotype 2.
authors.affiliation: Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan. tkumada@he.mirai.ne.jp
authors.forename: Hidenori
authors.initials: H
authors.lastname: Toyoda
authors.forename: Takashi
authors.initials: T
authors.lastname: Kumada
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Tada
authors.forename: Takahisa
authors.initials: T
authors.lastname: Kawaguchi
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Murakami
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Matsuda
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage*; D002888:Chromosomes, Human, Pair 19 / Q000737:chemistry* / Q000235:genetics; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D007564:Japan; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011110:Polymorphism, Genetic; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage; D016896:Treatment Outcome; D014758:Viral Core Proteins / Q000235:genetics*; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D014758:Viral Core Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a