title: N-acetyltransferase 2 polymorphisms and risk of anti-tuberculosis drug-induced hepatotoxicity in Caucasians.
abstract: OBJECTIVE
  To analyse slow-acetylation N-acetyltransferase 2 (NAT2) polymorphisms for their association with the risk of anti-tuberculosis drug-induced hepatotoxicity (ATDH).
  
  
  METHODS
  A case-control study including Caucasian patients with tuberculosis (TB) treated with isoniazid, rifampicin and pyrazinamide. NAT2 genotype results were compared between ATDH cases and controls and with a healthy Spanish control population of Caucasian origin.
  
  
  RESULTS
  Fifty cases and 67 controls were included in the study. Slow, intermediate and rapid NAT2 genotypes were found in respectively 72%, 18% and 10% of cases compared with 65.7%, 25.4% and 9% of controls (P> 0.05). On comparing NAT2 genotypes among cases with those among healthy controls (n = 1312), we found more slow NAT2 genotypes and fewer intermediate genotypes among cases (respectively 72% and 18% in cases vs. 54.8% and 38.1% in controls; OR 2.07, 95%CI 1.12-2.79, P = 0.016 and OR 0.37, 95%CI 0.18-0.75, P = 0.003).
  
  
  CONCLUSIONS
  We could not demonstrate an increased risk of ATDH related to the presence of slow NAT2 polymorphisms among this Caucasian TB cohort. However, we found a significantly greater frequency of slow and a significantly lower frequency of intermediate NAT2 genotypes among the ATDH cases compared with the healthy control population.
authors.affiliation: Servicio de Neumología, Complexo Hospitalario Universitario de Vigo (CHUVI), Vigo, Spain. virginia.leiro.fernandez@sergas.es
authors.forename: V
authors.initials: V
authors.lastname: Leiro-Fernandez
authors.forename: D
authors.initials: D
authors.lastname: Valverde
authors.forename: R
authors.initials: R
authors.lastname: Vázquez-Gallardo
authors.forename: M
authors.initials: M
authors.lastname: Botana-Rial
authors.forename: L
authors.initials: L
authors.lastname: Constenla
authors.forename: J A
authors.initials: JA
authors.lastname: Agúndez
authors.forename: A
authors.initials: A
authors.lastname: Fernández-Villar
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000009:adverse effects* / Q000378:metabolism; D001191:Arylamine N-Acetyltransferase / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007538:Isoniazid / Q000009:adverse effects / Q000378:metabolism; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic; D011718:Pyrazinamide / Q000009:adverse effects / Q000378:metabolism; D012293:Rifampin / Q000009:adverse effects / Q000378:metabolism; D018570:Risk Assessment; D012307:Risk Factors; D014376:Tuberculosis / Q000188:drug therapy*; D044465:White People / Q000235:genetics*
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; D007538:Isoniazid; D012293:Rifampin