title: Hepatitis C virus genotype 1: how genetic variability of the core protein affects the response to pegylated-interferon and ribavirin therapy.
abstract: Hepatitis C virus subgenotypes 1a and 1b are found worldwide and cause 60% of all hepatitis C cases. It has been reported recently that viral genetic variations have a critical impact on the patient treatment outcome. In particular, polymorphisms of the HCV core protein have been linked to poor treatment response. However, most of these studies were conducted on Asian populations, Japanese in particular who are infected with HCV subgenotype 1b. Hence, we aimed in this study to examine the core protein polymorphisms in Saudi patients who are infected with chronic HCV genotype 1 (1a and 1b subtypes) and its association with treatment outcome. Direct sequencing of full-length core protein and data mining analyses were utilized. Results have shown that the response to treatment is dependent on subgenotypes. Indeed, HCV-1b showed different point mutations that are associated with treatment outcome where the point mutations at positions 70 (Arg(70) Gln) and 75 (Thr(75) Ala) in HCV-1b are significantly associated with PEG-IFN/RBV treatment response. In contrast, HCV-1a showed no significant association between core protein mutations and response to treatment. In addition, analyses of HCV-1a core protein sequences revealed a highly conserved region especially in the responder group. This study provides a new insight in the genetic variability of full-length core protein in HCV genotype 1 in Saudi infected patients.
authors.affiliation: Department of Infection and Immunity, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: F S
authors.initials: FS
authors.lastname: Alhamlan
authors.forename: M N
authors.initials: MN
authors.lastname: Al-Ahdal
authors.forename: N Z
authors.initials: NZ
authors.lastname: Khalaf
authors.forename: A A
authors.initials: AA
authors.lastname: Abdo
authors.forename: F M
authors.initials: FM
authors.lastname: Sanai
authors.forename: H I
authors.initials: HI
authors.lastname: Al-Ashgar
authors.forename: M
authors.initials: M
authors.lastname: Elhefnawi
authors.forename: A
authors.initials: A
authors.lastname: Zaid
authors.forename: A A
authors.initials: AA
authors.lastname: Al-Qahtani
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D019295:Computational Biology; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D012254:Ribavirin / Q000627:therapeutic use*; D012529:Saudi Arabia; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome; D014758:Viral Core Proteins / Q000235:genetics*
chemical_list: D000998:Antiviral Agents; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D012254:Ribavirin; D007372:Interferons
keywords: PEG-IFN/RBV therapy; Saudi Arabia; genotype 1; hepatitis C virus; sustained virological response