title: Mutations in the NS5A gene of hepatitis C virus subtype 1b and response to peg-IFNα-2a/RBV combination therapy in Azerbaijani patients.
abstract: Hepatitis C virus (HCV) infection is one of the major causes of chronic liver disease throughout the world. The presence of mutations in different regions of the HCV subtype 1b (HCV-1b) nonstructural 5A (NS5A) gene may be associated with response to interferon therapy. This study evaluated whether amino acid substitutions in the NS5A protein of HCV-1b correlated with response to pegylated interferon alfa-2a (peg-IFNα-2a) and ribavirin (RBV) combination therapy in Azerbaijani patients. From March 2010 to April 2014, a total of 34 chronically HCV-1b-infected Azerbaijani patients were enrolled in this prospective study. After extraction of RNA from plasma specimens, the entire sequences of the NS5A gene of HCV was amplified by reverse transcription nested polymerase chain reaction (RT-nested PCR), and the PCR products were sequenced subsequently. The data that were obtained revealed that there was no correlation between the response to HCV combination therapy and the number of mutations in the NS5A-PKRBD, NS5A-ISDR, and NS5A-V3 regions of HCV. It also was found that changes from isoleucine to valine (I2252 V), aspartic acid to glutamic acid (D2257), arginine to lysine (R2269 K), and arginine to glycine in NS5A-PKRBD and from glycine to glutamic acid (G2379E) in the NS5A-V3 region were not associated with HCV treatment outcome. This study showed that genetic variability in the NS5A-PKRBD, NS5A-ISDR, and NS5A-V3 regions is not a predictive factor of SVR, NR or relapse in HCV genotype1b treated with peg-IFNα-2a/RBV combination therapy.
authors.affiliation: Department of Virology, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Farah
authors.initials: F
authors.lastname: Bokharaei-Salim
authors.forename: Hossein
authors.initials: H
authors.lastname: Keyvani
authors.forename: Mostafa
authors.initials: M
authors.lastname: Salehi-Vaziri
authors.forename: Farzin
authors.initials: F
authors.lastname: Sadeghi
authors.forename: Seyed Hamidreza
authors.initials: SH
authors.lastname: Monavari
authors.forename: Leila
authors.initials: L
authors.lastname: Mehrnoush
authors.forename: Seyed Moayed
authors.initials: SM
authors.lastname: Alavian
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000627:therapeutic use*; D001382:Azerbaijan / Q000453:epidemiology; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification*; D006526:Hepatitis C / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use*; D016415:Sequence Alignment; D016896:Treatment Outcome; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000235:genetics*; D055815:Young Adult; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C100416:peginterferon alfa-2a