title: Hepatitis C virus genotype 1a NS5A pretreatment sequence variation and viral kinetics in African American and white patients.
abstract: In hepatitis C virus (HCV) infection, race is a determinant of treatment response and interferon (IFN) effectiveness. Here, we investigated whether there were differences in the pretreatment viral strains between African American patients and white patients and whether these differences correlated with viral kinetics. IFN effectiveness was calculated using a viral kinetic model. The HCV NS5A region from 21 treated patients with HCV genotype 1a was sequenced and analyzed. White patients displayed more mutations in the V3 region (mean+/-SD, 4.5+/-1.4 vs. 2.9+/-1.6; P=.016), and treatment responders tended to have more mutations in this region than did nonresponders. There was a significant positive correlation between IFN effectiveness and the number of mutations in the V3 region (P=.03). There was no clustering of strains by race, treatment response, or IFN effectiveness in phylogenetic analyses. The results of this study, in conjunction with those of a previous study illustrating the impaired IFN effectiveness in African Americans, suggest a role for host-related factors.
authors.affiliation: Department of Medicine, University of Illinois at Chicago, 60612, USA. jlayde1@uic.edu
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Layden-Almer
authors.forename: Carla
authors.initials: C
authors.lastname: Kuiken
authors.forename: Ruy M
authors.initials: RM
authors.lastname: Ribeiro
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Kunstman
authors.forename: Alan S
authors.initials: AS
authors.lastname: Perelson
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Layden
authors.forename: Steven M
authors.initials: SM
authors.lastname: Wolinsky
mesh_terms: D001741:Black or African American; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000494:pharmacology; D014644:Genetic Variation; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D006526:Hepatitis C / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D007372:Interferons / Q000494:pharmacology; D007700:Kinetics; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D017422:Sequence Analysis, DNA; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D044465:White People; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D007372:Interferons; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase