Pharmacogenetics of Isoniazid-induced Hepatotoxicity

Perwitasari, Dyah Aryani and Atthobari, Jarir and Wilffert, Bob (2015) Pharmacogenetics of Isoniazid-induced Hepatotoxicity. Drug Metabolism Reviews, 47 (2). pp. 222-228. ISSN 1097-9883 / 0360-2532


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Tuberculosis is still a major problem in some developed and developing countries. The poor compliance to the treatment of tuberculosis patients due to the adverse events was supposed to be an important factor contributing to the high prevalence. This review aims to clarify the role and the pharmacological mechanism of the genes involved in the isoniazid-induced hepatotoxicity. We selected English articles of studies in human from PubMed up to May 2014 with the keywords pharmacogenetic, isoniazid and hepatotoxicity, N-acetyl transferase 2 (NAT2), CYP2E1 and glutathione S transferase (GST). Polymorphisms of NAT2, CYP2E1 and GST1 could increase patients’ susceptibility to isoniazid-induced hepatotoxicity. The rapid acetylators of NAT2 and rapid metabolizers of CYP2E1 showed increased concentrations of hepatotoxic metabolites. However, the rapid metabolizers of GST1 could decrease the concentration of hepatotoxic metabolites. Some studies of human leukocyte antigen (HLA), Uridine 50-dipphospho (UDP) glucuronosyltransferase (UGT), nitric oxide synthase (NOS), Broad complex, Tramtrack, Bric-a-brac (BTB) and cap’n’collar type of basic region leucine zipper factor family (CNC) homolog (BACH) and Maf basic leucine zipper protein (MAFK) polymorphisms showed their roles in isoniazid-induced hepatotoxicity by modifying the expression of antioxidant enzymes. A better insight into the role of polymorphisms of HLA, UGT, NOS, BACH and MAFK in addition to NAT2, CYP2E1 and GST1 in the hepatotoxicity of isoniazid may support physicians in monitoring patients hepatotoxicity symptoms and laboratory data and optimizing pharmacotherapy. Future studies about the role of such polymorphisms in different ethnicities are suggested.

Item Type: Article
Subjects: R Medicine > RS Pharmacy and materia medica
Divisions: Faculty of Pharmacy (Fakultas Farmasi) > Pharmacy Doc
Depositing User: dyah aryani
Date Deposited: 28 Aug 2017 02:08
Last Modified: 28 Aug 2017 02:08

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