NAT2 Genotypes in Moroccan Patients with Hepatotoxicity Due to Antituberculosis Drugs.
| Autor: | Guaoua S; 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 ., Ratbi I; 1 Centre de Génomique Humaine, Faculté de Médecine et de Pharmacie, Université Mohammed V , Rabat, Morocco ., El Bouazzi O; 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 ., Hammi S; 5 Faculte de Médecine, Université Abdel Malek Essaadi , Tanger, Morocco ., Tebaa A; 3 Laboratoire de Pharmacotoxicologie, Centre Anti Poison et de Pharmacovigilance, Faculté de Médecine et de Pharmacie, Université Mohammed V , Rabat, Morocco ., Bourkadi JE; 6 Département de Pneumologie, Hôpital Moulay Youssef - Centre Hospitalier Ibn Sina Rabat, Faculté de Médecine et de Pharmacie, Université Mohammed V, Rabat, Morocco ., Bencheikh RS; 3 Laboratoire de Pharmacotoxicologie, Centre Anti Poison et de Pharmacovigilance, Faculté de Médecine et de Pharmacie, Université Mohammed V , Rabat, Morocco ., Sefiani A; 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 . |
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| Jazyk: | angličtina |
| Zdroj: | Genetic testing and molecular biomarkers [Genet Test Mol Biomarkers] 2016 Nov; Vol. 20 (11), pp. 680-684. Date of Electronic Publication: 2016 Aug 19. |
| DOI: | 10.1089/gtmb.2016.0060 |
| Abstrakt: | Aim: 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. Patients and 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. Conclusion: 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. |
| Databáze: | MEDLINE |
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