title: Association of the CYP2B6 gene with anti-tuberculosis drug-induced hepatotoxicity in a Brazilian Amazon population.
abstract: OBJECTIVE
  The treatment of tuberculosis (TB) remains a challenge owing to the high incidence of drug-induced hepatotoxicity. The aim of this study was to examine the effect of two gene polymorphisms, one in the CYP2B6 (rs3745274) gene and one in the CYP3A5 (rs776746) gene, on the development of hepatotoxicity in patients treated with anti-TB drugs in a Brazilian Amazon population.
  
  
  METHODS
  TB patients who were treated with anti-TB drugs were examined for hepatotoxicity, an adverse effect that is characterized by liver damage. The genotype frequencies of the CYP2B6 and CYP3A5 genes examined in this study were assessed using RT-PCR.
  
  
  RESULTS
  Thirty-one of the 220 subjects (14.1%) included in this study developed drug-induced hepatotoxicity. The result was significant when the TT homozygous mutant of the CYP2B6 gene was analyzed with additional key variables (p=0.046; odds ratio (OR) 0.063, 95% confidence interval (CI) 0.004-0.955), which may explain the hepatotoxicity results in this study. Using a univariate statistical model to associate the CYP3A5 gene A6986G polymorphism with the examined drugs, the results did not differ between samples from individuals with and without hepatotoxicity (p=0.176; OR 0.562, 95% CI 0.255-1.238).
  
  
  CONCLUSIONS
  The G516T polymorphism in the CYP2B6 gene is a key predictor of the therapeutic response to treatment in TB patients.
authors.affiliation: Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Universidade Federal do Pará, CEP 66075-970 Belém, Pará, Brazil; Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Pará, Brazil.
authors.forename: Débora Christina Ricardo Oliveira
authors.initials: DC
authors.lastname: Fernandes
authors.affiliation: Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Universidade Federal do Pará, CEP 66075-970 Belém, Pará, Brazil; Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Pará, Brazil.
authors.forename: Ney Pereira Carneiro
authors.initials: NP
authors.lastname: Santos
authors.affiliation: Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Universidade Federal do Pará, CEP 66075-970 Belém, Pará, Brazil.
authors.forename: Milene Raiol
authors.initials: MR
authors.lastname: Moraes
authors.affiliation: Hospital João de Barros Barreto, Universidade Federal do Pará, Belém, Pará, Brazil.
authors.forename: Ana Cristina Oliveira
authors.initials: AC
authors.lastname: Braga
authors.affiliation: Hospital João de Barros Barreto, Universidade Federal do Pará, Belém, Pará, Brazil.
authors.forename: Cleonardo Augusto
authors.initials: CA
authors.lastname: Silva
authors.affiliation: Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Universidade Federal do Pará, CEP 66075-970 Belém, Pará, Brazil; Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Pará, Brazil.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ribeiro-dos-Santos
authors.affiliation: Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Universidade Federal do Pará, CEP 66075-970 Belém, Pará, Brazil; Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Pará, Brazil. Electronic address: sidneysantos@ufpa.br.
authors.forename: Sidney
authors.initials: S
authors.lastname: Santos
mesh_terms: D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001938:Brazil; D065702:Cytochrome P-450 CYP2B6 / Q000235:genetics*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008099:Liver / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014376:Tuberculosis / Q000188:drug therapy* / Q000235:genetics
chemical_list: D000995:Antitubercular Agents; D065702:Cytochrome P-450 CYP2B6; D051544:Cytochrome P-450 CYP3A
keywords: CYP2B6; CYP3A5; Hepatotoxicity; Tuberculosis