title: IL28B polymorphisms are markers of therapy response and are influenced by genetic ancestry in chronic hepatitis C patients from an admixed population.
abstract: BACKGROUND
  IL28B polymorphisms are predictors of therapy response in hepatitis C virus (HCV) patients. We do not know whether they are markers of treatment response in admixed populations or not.
  
  
  OBJECTIVE
  To determine whether IL28B polymorphisms are predictors of therapy response in patients with HCV from an admixed population and are influenced by genetic ancestry.
  
  
  METHODS
  rs12979860 and rs8099917 were genotyped in 222 HCV patients treated with pegylated interferon and ribavirin. Ancestry was determined using genetic markers.
  
  
  RESULTS
  IL28B rs12979860 C/C was associated with sustained virological response (SVR), whereas C/T and T/T were associated with failure to therapy (P = 1.12 × 10(-5) ). IL28B rs8099917 T/T was associated with SVR, and G/G and G/T were associated with nonresponse/relapse (NR/R) (P = 8.00 × 10(-3) ). Among HCV genotype 1 patients with C/C genotype, genomic ancestry did not interfere with therapy response. Among patients with rs12979860 T/T genotype, African genetic contribution was greater in the NR/R group (P = 1.51 × 10(-3) ), whereas Amerindian and European genetic ancestry contribution were higher in the SVR group (P = 3.77 × 10(-3) and P = 2.16 × 10(-2) respectively). Among HCV type 1 patients with rs8099917 T/T, African genetic contribution was significantly greater in the NR/R group (P = 5.0 × 10(-3) ); Amerindian and European ancestry genetic contribution were greater in the SVR group.
  
  
  CONCLUSIONS
  IL28B rs12979860 and rs8099917 polymorphisms were predictors of therapy response in HCV genotypes 1, 2 and 3 subjects from an admixed population. Genomic ancestry did not interfere with response to therapy in patients with rs12979860 C/C, whereas it interfered in patients with C/T and T/T genotypes. Among HCV genotype 1 rs8099917 T/T patients, genomic ancestry interfered with response to therapy.
authors.affiliation: Department of Medicine, Federal University of Bahia, Salvador, Bahia, Brazil.
authors.forename: Lourianne N
authors.initials: LN
authors.lastname: Cavalcante
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Abe-Sandes
authors.forename: Ana Luiza D
authors.initials: AL
authors.lastname: Angelo
authors.forename: Taisa M B
authors.initials: TM
authors.lastname: Machado
authors.forename: Denise C
authors.initials: DC
authors.lastname: Lemaire
authors.forename: Carlos M C
authors.initials: CM
authors.lastname: Mendes
authors.forename: João R
authors.initials: JR
authors.lastname: Pinho
authors.forename: Fernanda
authors.initials: F
authors.lastname: Malta
authors.forename: Luiz G C
authors.initials: LG
authors.lastname: Lyra
authors.forename: André C
authors.initials: AC
authors.lastname: Lyra
mesh_terms: D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers / Q000235:genetics*; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044469:Racial Groups / Q000235:genetics; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use*; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D019562:Viral Load; D000095022:Interferon Lambda
chemical_list: D005819:Genetic Markers; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C100416:peginterferon alfa-2a