title: Myxovirus resistance, osteopontin and suppressor of cytokine signaling 3 polymorphisms predict hepatitis C virus therapy response in an admixed patient population: comparison with IL28B.
abstract: OBJECTIVE
  Suppressor of cytokine signaling 3, myxovirus resistance protein and osteopontin gene polymorphisms may influence the therapeutic response in patients with chronic hepatitis C, and an association with IL28 might increase the power to predict sustained virologic response. Our aims were to evaluate the association between myxovirus resistance protein, osteopontin and suppressor of cytokine signaling 3 gene polymorphisms in combination with IL28B and to assess the therapy response in hepatitis C patients treated with pegylated-interferon plus ribavirin.
  
  
  METHODS
  Myxovirus resistance protein, osteopontin, suppressor of cytokine signaling 3 and IL28B polymorphisms were analyzed by PCR-restriction fragment length polymorphism, direct sequencing and real-time PCR. Ancestry was determined using genetic markers.
  
  
  RESULTS
  We analyzed 181 individuals, including 52 who were sustained virologic responders. The protective genotype frequencies among the sustained virologic response group were as follows: the G/G suppressor of cytokine signaling 3 (rs4969170) (62.2%); T/T osteopontin (rs2853744) (60%); T/T osteopontin (rs11730582) (64.3%); and the G/T myxovirus resistance protein (rs2071430) genotype (54%). The patients who had ≥3 of the protective genotypes from the myxovirus resistance protein, the suppressor of cytokine signaling 3 and osteopontin had a greater than 90% probability of achieving a sustained response (p<0.0001). The C/C IL28B genotype was present in 58.8% of the subjects in this group. The sustained virological response rates increased to 85.7% and 91.7% by analyzing C/C IL28B with the T/T osteopontin genotype at rs11730582 and the G/G suppressor of cytokine signaling 3 genotype, respectively. Genetic ancestry analysis revealed an admixed population.
  
  
  CONCLUSIONS
  Hepatitis C genotype 1 patients who were responders to interferon-based therapy had a high frequency of multiple protective polymorphisms in the myxovirus resistance protein, osteopontin and suppressor of cytokine signaling 3 genes. The combined analysis of the suppressor of cytokine signaling 3 and IL28B genotypes more effectively predicted sustained virologic response than IL28B analysis alone.
authors.affiliation: Laboratory of Immunology, Federal University of Bahia, SalvadorBA, Brazil.
authors.forename: Ana Luiza Dias
authors.initials: AL
authors.lastname: Angelo
authors.forename: Lourianne Nascimento
authors.initials: LN
authors.lastname: Cavalcante
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Abe-Sandes
authors.forename: Taísa Bonfim
authors.initials: TB
authors.lastname: Machado
authors.forename: Denise Carneiro
authors.initials: DC
authors.lastname: Lemaire
authors.forename: Fernanda
authors.initials: F
authors.lastname: Malta
authors.forename: João Renato
authors.initials: JR
authors.lastname: Pinho
authors.forename: Luiz Guilherme Costa
authors.initials: LG
authors.lastname: Lyra
authors.forename: Andre Castro
authors.initials: AC
authors.lastname: Lyra
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D064547:Myxovirus Resistance Proteins / Q000187:drug effects / Q000235:genetics*; D053495:Osteopontin / Q000187:drug effects / Q000235:genetics*; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011110:Polymorphism, Genetic / Q000235:genetics*; D011237:Predictive Value of Tests; D060888:Real-Time Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000187:drug effects / Q000235:genetics*; D016896:Treatment Outcome; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D005819:Genetic Markers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D064547:Myxovirus Resistance Proteins; D053495:Osteopontin; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C106644:SOCS3 protein, human; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a