title: Interleukin 28B-related polymorphisms: a pathway for understanding hepatitis C virus infection?
abstract: OBJECTIVE
  To analyze the role of rs12979860 and rs8099917 polymorphisms in hepatitis C virus (HCV) genotype 1 infection of Brazilians.
  
  
  METHODS
  A total of 145 adult patients diagnosed with genotype 1 chronic hepatitis C (CHC) who had completed a 48-wk regimen of pegylated-interferon α-2a or -2b plus ribavirin combination therapy were recruited from six large urban healthcare centers and 199 healthy blood donors (controls) from a single site between January 2010 and January 2012. Data on the patients' response to treatment was collected. Polymerase chain reaction-restriction fragment length polymorphism genotyping of the interleukin (IL)28B gene fragment encompassing the single nucleotide polymorphisms (SNPs) rs12979860 (C/T) and rs8099917 (T/G) was carried out for 79 of the CHC patients and 199 of the controls. Bi-directional amplicon sequencing of the two SNPs was carried out for the remaining 66 CHC patients.
  
  
  RESULTS
  SNP rs12979860 genotyping was successful in 99.5% of the controls and 97.2% of the CHC patients, whereas the SNP rs8099917 genotyping was successful in 95.5% of the controls and 100% of the CHC patients. The genotype and allele distributions for both rs12979860 and rs8099917 were significantly different between the control and CHC patient groups, with significantly higher genotype frequencies of CC and TT in the controls (P = 0.037 and 0.046, respectively) and of TT and GG in the CHC patients (P = 0.0009 and 0.0001, respectively). Analysis of the CHC patients who achieved sustained virological response (SVR) to treatment (n = 55) indicated that the rs12979860 C allele and CC genotype were predictors of SVR (P = 0.02). No significant correlation was found between rs8099917 genotypes and treatment response, but carriers of the T allele showed significantly higher rates of SVR (P = 0.02). Linkage disequilibrium analysis of the group that achieved SVR showed a significant association between rs12979860 and rs8099917 (P = 0.07).
  
  
  CONCLUSIONS
  The higher allele frequency of rs12979860 C and rs8099917 T observed in non-HCV-infected individuals may indicate a potential protective role for these IL28B-related polymorphisms.
authors.affiliation: Raquel Francine Liermann Garcia, Simone Moreira, Leslie Ecker Ferreira, Christian Evangelista Garcia, Mauro de Souza Leite Pinho, Paulo Henrique Condeixa de França, Departamento de Medicina, Universidade da Região de Joinville/Univille, Joinville, 89219-719 Santa Catarina, Brazil.
authors.forename: Raquel Francine Liermann
authors.initials: RF
authors.lastname: Garcia
authors.forename: Simone
authors.initials: S
authors.lastname: Moreira
authors.forename: Ana Lucia
authors.initials: AL
authors.lastname: de Araújo Ramos
authors.forename: Leslie Ecker
authors.initials: LE
authors.lastname: Ferreira
authors.forename: Angelo Alves
authors.initials: AA
authors.lastname: de Mattos
authors.forename: Cristiane Valle
authors.initials: CV
authors.lastname: Tovo
authors.forename: Lysandro Alsina
authors.initials: LA
authors.lastname: Nader
authors.forename: Juliene Antonio
authors.initials: JA
authors.lastname: Ramos
authors.forename: Edson
authors.initials: E
authors.lastname: Rondinelli
authors.forename: Arnaldo
authors.initials: A
authors.lastname: de Jesus Dominici
authors.forename: Christian Evangelista
authors.initials: CE
authors.lastname: Garcia
authors.forename: Mauro
authors.initials: M
authors.lastname: de Souza Leite Pinho
authors.forename: Carlos Eduardo
authors.initials: CE
authors.lastname: Brandão-Mello
authors.forename: Cristiane Alves
authors.initials: CA
authors.lastname: Villela-Nogueira
authors.forename: Paulo Henrique Condeixa
authors.initials: PH
authors.lastname: de França
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D001938:Brazil; D016022:Case-Control Studies; D004359:Drug Therapy, Combination; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011092:Polyethylene Glycols / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a
keywords: Brazil; Hepatitis C; Interleukin 28B; Single nucleotide polymorphisms; Sustained virological response