title: Core mutations, IL28B polymorphisms and response to peginterferon/ribavirin treatment in Swedish patients with hepatitis C virus genotype 1 infection.
abstract: BACKGROUND
  Patients infected with hepatitis C virus (HCV) genotype 1 respond poorly to standard treatment with 50% or less achieving sustained virologic response. Predicting outcome is essential and could help avoid unnecessary treatment and reduce health cost. Recently, an association of amino acid substitutions in the core region and treatment outcome was observed in Japanese patients. In the present study, the impact of these mutations on response kinetics and treatment outcome was explored in Caucasian patients.
  
  
  METHODS
  The core region of HCV pre-treatment samples obtained from 50 patients treated with peginterferon/ribavirin in a previous Swedish clinical trial with genotype 1 infection were sequenced. The alleles at rs12979860, a single nucleotide polymorphism (SNP), were assessed in order to identify any co-association with this strong response predictor.
  
  
  RESULTS
  No association between treatment response and substitutions of core residue 91 was found. In contrast, substitutions of core residue 70 were observed in 6/21 (29%) non-responders, but only in one of 29 responders (p = 0.03), and were more common in subgenotype 1b (R70Q in 6 of 13 strains) than in 1a (R70P in 1 of 37 strains, p = 0.004). The rs12979860 SNP upstream of the IL28B gene was overall the strongest response predictor (p = 0.0001). Core 70 substitutions were associated with poorer response kinetics in patients carrying the CT genotype at rs12979860.
  
  
  CONCLUSIONS
  The results indicate that substitutions of core residue 70 are related to treatment response in Caucasian patients with HCV-1b infection, but are of less importance than IL28B polymorphism.
authors.affiliation: Department of Infection and Virology, University of Gothenburg, Gothenburg, Sweden. erik.alestig@gu.se
authors.forename: Erik
authors.initials: E
authors.lastname: Alestig
authors.forename: Birgitta
authors.initials: B
authors.lastname: Arnholm
authors.forename: Anders
authors.initials: A
authors.lastname: Eilard
authors.forename: Martin
authors.initials: M
authors.lastname: Lagging
authors.forename: Staffan
authors.initials: S
authors.lastname: Nilsson
authors.forename: Gunnar
authors.initials: G
authors.lastname: Norkrans
authors.forename: Thomas
authors.initials: T
authors.lastname: Wahlberg
authors.forename: Rune
authors.initials: R
authors.lastname: Wejstål
authors.forename: Johan
authors.initials: J
authors.lastname: Westin
authors.forename: Magnus
authors.initials: M
authors.lastname: Lindh
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D006526:Hepatitis C / Q000188:drug therapy* / Q000235:genetics* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use*; D013548:Sweden; D016896:Treatment Outcome; D014758:Viral Core Proteins / Q000235:genetics*; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; D014758:Viral Core Proteins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C100416:peginterferon alfa-2a