GENOTYPE POLYMORPHISMS OF NAT2 AND CYP2E1 GENES ASSOCIATED WITH DRUG INDUCED LIVER INJURY (DILI) IN INDONESIAN TUBERCULOSIS PATIENTS
| Autor: | Jarir Atthobari, Dyah Aryani Perwitasari, Ully Adhie Mulyani, Malinda Noverliyanti, Endang Darmawan, Bob Wilffert |
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| Přispěvatelé: | Reproductive Origins of Adult Health and Disease (ROAHD), PharmacoTherapy, -Epidemiology and -Economics, Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET) |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
medicine.medical_specialty
isoniazid Tuberculosis Pharmaceutical Science lcsh:RS1-441 Single-nucleotide polymorphism Pharmacy Pharmacology Gastroenterology lcsh:Pharmacy and materia medica 03 medical and health sciences 0302 clinical medicine Internal medicine Genotype medicine Pharmacology (medical) 030212 general & internal medicine CYP2E1 ANTITUBERCULOSIS DRUGS Liver injury business.industry Isoniazid medicine.disease NAT2 INDIAN POPULATION tuberculosis Indonesia N-ACETYLTRANSFERASE 030220 oncology & carcinogenesis ISONIAZID-INDUCED HEPATOTOXICITY Liver function business Cohort study medicine.drug |
| Zdroj: | Indonesian Journal of Pharmacy, Vol 27, Iss 1, Pp 1-6 (2016) Indonesian journal of pharmacy, 27(1), 22-27. UNIV GADJAH MADA, FAC FARMASI |
| ISSN: | 2338-9486 |
| DOI: | 10.14499/indonesianjpharm27iss1pp22 |
| Popis: | Currently, Indonesia is in the fifth rank of highest TB prevalence over the world. One of the TB problem is low patients’ adherence due to the oral antituberculosis induced hepatotoxicity. Polymorphisms of NAT2 and CYP2E1 genes had important role in the isoniazid (INH)-induced hepatotoxicity. The aim of this study was to evaluate the polymorphisms profile of NAT2 and CYP2E1 genes associated with hepatotoxicity induced by INH. We used cohort design in Public Health Centers and Lung Clinics of Yogyakarta and Lampung. The inclusion criteria were adult subjects (> 18 yo), newly diagnosed TB and treated by oral antituberculosis, normal function of renal and live and willingness to participate in this study. Subjects were excluded when having positive reaction of HbsAg test, history of HIV and abnormality of renal and liver function. The SNPs of NAT2 and CYP2E1 were designed using IPlex method of DNA sequenom. Among 57 TB patients, we found 14 patients with higher INH serum concentration and experienced increase of ALT-AST. Subjects with SNPs of rs 2070676, rs 1329149, rs 3813867, rs 6413432, rs 8192772, rs 2031920, rs 2515641, rs 8192775, rs 915908 of CYP2E1 experienced increase of ALT and AST . Subjects with SNPs of rs 1799930, rs1799931, rs1801279, rs1801280, rs1799929 , rs1208, rs1041983 of NAT2 are associated with the increase of ALT and AST . The polymorphisms of CYP2E1 and NAT2 may have a role in the mechanisms of INH induced DILI. Keywords: CYP2E1, NAT2, tuberculosis, isoniazid, Indonesia |
| Databáze: | OpenAIRE |
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