title: The roles of GSTM1 and GSTT1 null genotypes and other predictors in anti-tuberculosis drug-induced liver injury.
abstract: OBJECTIVE
  Anti-tuberculosis drugs (ATD), although highly effective, often cause liver injury. Glutathione S-transferases (GST) play a crucial protective role in the detoxifying mechanisms of drugs. Several studies have investigated the genetic null variants of GSTM1 and GSTT1 as possible risk factors for ATD-induced liver injury; however, those findings are inconsistent. We investigated GSTM1 and GSTT1 null genotypes in Brazilian patients with tuberculosis (TB), adjusting for other possible predictors of ATD-induced liver injury.
  
  
  METHODS
  This was a prospective cohort study with patients who were treated for TB from 2006 to 2011. GSTM1 and GSTT1 gene deletions were analysed from genomic DNA by polymerase chain reaction (PCR). Demographic, clinical and laboratory data were extracted from medical records and possible predictors of liver injury were evaluated.
  
  
  CONCLUSIONS
  This study enrolled 177 patients. Anti-tuberculosis drugs-induced liver injury incidence was 33.3%. Hepatitis B infection (HBV) and increased alanine aminotransferase (ALT) baseline were significant predictors. Neither GSTM1 nor GSTT1 null genotypes were associated with ATD-induced liver injury; nevertheless, the comparison among four different liver toxicity grades showed that GSTM1 non-null genotype was significant more frequent among the higher grades of liver toxicity.
  
  
  CONCLUSIONS
  GSTM1 and GSTT1 null genotypes do not seem to play important roles in ATD-induced liver injury in Brazilians. However, there was evidence that GSTM1 polymorphisms were possibly related to the intensity of toxicity. Active HBV and initial high ALT could predict ATD-induced liver injury.
authors: Pharmacogenetics Research Laboratory, Evandro Chagas Clinical Research Institute, Oswaldo Cruz Foundation, Rio de Janeiro, RJ, Brazil.
authors: T P
authors: TP
authors: Monteiro
authors: K B
authors: KB
authors: El-Jaick
authors: A L
authors: AL
authors: Jeovanio-Silva
authors: P E A A
authors: PE
authors: Brasil
authors: M J M
authors: MJ
authors: Costa
authors: V C
authors: VC
authors: Rolla
authors: L
authors: L
authors: de Castro
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000009:adverse effects*; D001938:Brazil / Q000453:epidemiology; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012307:Risk Factors; D014376:Tuberculosis / Q000188:drug therapy
chemical_list: D000995:Antitubercular Agents; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1