title: NAT2 Genotypes in Moroccan Patients with Hepatotoxicity Due to Antituberculosis Drugs.
abstract: OBJECTIVE
  Isoniazid (INH) is the most effective drug used as a first-line tuberculosis (TB) treatment besides rifampicin, pyrazinamide, and ethambutol. It is also the most commonly associated with hepatotoxicity. Differences of toxicity induced by INH have been attributed to genetic variability of the N-acetyltransferase 2 (NAT2) gene which encodes a drug-metabolizing enzyme. The aim of this study was to characterize the acetylation profile of patients who developed hepatotoxicity after TB treatment by genotyping NAT2 polymorphisms.
  
  
  METHODS
  This study included 42 Moroccan patients who developed hepatotoxicity after TB treatment and 163 Moroccan controls without TB. We genotyped four selected variants of the NAT2 gene (NAT2*5, NAT2*6, NAT2*7, and NAT2*14) by Sanger sequencing for patients and real-time polymerase chain reaction for controls.
  
  
  RESULTS
  The majority of patients had NAT2 genotypes previously described as slow acetylators including NAT2*5/*5, NAT2*5/*6, NAT2*6/*6, and NAT2*6/*14 (78%) and none were genotyped as rapid acetylators. Controls were slow, intermediate, and rapid acetylators with frequencies of 72.39%, 21.48%, and 6.13%, respectively.
  
  
  CONCLUSIONS
  There were no fast acetylator genotypes found among the patients having INH-hepatotoxicity. This finding suggests that the slow acetylator phenotype may contribute to the development of TB treatment hepatotoxicity.
authors.affiliation: 1 Centre de Génomique Humaine, Faculté de Médecine et de Pharmacie, Université Mohammed V , Rabat, Morocco .|2 Département de Génétique Médicale, Institut National d'Hygiène , Rabat, Morocco .
authors.forename: Soukaina
authors.initials: S
authors.lastname: Guaoua
authors.affiliation: 1 Centre de Génomique Humaine, Faculté de Médecine et de Pharmacie, Université Mohammed V , Rabat, Morocco .
authors.forename: Ilham
authors.initials: I
authors.lastname: Ratbi
authors.affiliation: 3 Laboratoire de Pharmacotoxicologie, Centre Anti Poison et de Pharmacovigilance, Faculté de Médecine et de Pharmacie, Université Mohammed V , Rabat, Morocco .|4 Faculté des Sciences, Université Ibn Tofail , Kénitra, Morocco .
authors.forename: Omaima
authors.initials: O
authors.lastname: El Bouazzi
authors.affiliation: 5 Faculte de Médecine, Université Abdel Malek Essaadi , Tanger, Morocco .
authors.forename: Sanaa
authors.initials: S
authors.lastname: Hammi
authors.affiliation: 3 Laboratoire de Pharmacotoxicologie, Centre Anti Poison et de Pharmacovigilance, Faculté de Médecine et de Pharmacie, Université Mohammed V , Rabat, Morocco .
authors.forename: Amina
authors.initials: A
authors.lastname: Tebaa
authors.affiliation: 6 Département de Pneumologie, Hôpital Moulay Youssef - Centre Hospitalier Ibn Sina Rabat, Faculté de Médecine et de Pharmacie, Université Mohammed V, Rabat, Morocco .
authors.forename: Jamal Eddine
authors.initials: JE
authors.lastname: Bourkadi
authors.affiliation: 3 Laboratoire de Pharmacotoxicologie, Centre Anti Poison et de Pharmacovigilance, Faculté de Médecine et de Pharmacie, Université Mohammed V , Rabat, Morocco .
authors.forename: Rachida Soulaymani
authors.initials: RS
authors.lastname: Bencheikh
authors.affiliation: 1 Centre de Génomique Humaine, Faculté de Médecine et de Pharmacie, Université Mohammed V , Rabat, Morocco .|2 Département de Génétique Médicale, Institut National d'Hygiène , Rabat, Morocco .
authors.forename: Abdelaziz
authors.initials: A
authors.lastname: Sefiani
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000995:Antitubercular Agents / Q000009:adverse effects*; D001191:Arylamine N-Acetyltransferase / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007538:Isoniazid / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009018:Morocco; D020641:Polymorphism, Single Nucleotide; D014376:Tuberculosis / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism
chemical_list: D000995:Antitubercular Agents; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; D007538:Isoniazid
keywords: Moroccan; NAT2; hepatotoxicity; tuberculosis; variant