Dyah A Perwitasari1, Lalu M Irham2, Endang Darmawan2, Ully A Mulyani3, J Atthobari4. 1. Postgraduate Program of Clinical Pharmacy, Faculty of Pharmacy, Ahmad Dahlan University, Jl prof Dr Soepomo, Janturan 55164, Yogyakarta, Indonesia. Electronic address: diahperwitasari2003@yahoo.com. 2. Postgraduate Program of Clinical Pharmacy, Faculty of Pharmacy, Ahmad Dahlan University, Jl prof Dr Soepomo, Janturan 55164, Yogyakarta, Indonesia. 3. National Institute for Health Research and Development, Jl. Percetakan Negara 29, Jakarta Pusat 10560, Jakarta, Indonesia. 4. Faculty of Medicine, Universitas Gadjah Mada, Jl. Farmako Sekip 55281, Yogyakarta, Indonesia.
Abstract
OBJECTIVE: A polymorphism of CYP2E1 may be directly associated with the development of INH hepatotoxicity. We conducted this study to evaluate the association between polymorphisms of CYP2E1, Isoniazid (INH) concentration and the acetylator status of INH in cases of Indonesian tuberculosis patients with drug-induced liver disease (DILI). METHODS: We conducted our study with a cohort design consisting of 55 Indonesian adult tuberculosis (TB) patients. Acetylating phenotypes were studied in using the metabolic ratio of plasma AcHZ/HZ. DILI was defined using CTCAV version 4.0. The allelic and genotypic frequency distributions of CYP2E1 rs 3813867 were studied using the polymerase chain reaction - amplification refractory mutation system (ARMS) methodology. RESULTS: Patients with an INH concentration of more than 7μg/mL showed a higher risk of developing DILI when compared with patients who showed a therapeutic range of 3-6μg/mL INH (OR: 1.3, 95% CI: 0.2-8.2). Slow acetylators had a higher incidence of DILI when compared with rapid acetylators (OR: 4.6, 95% CI: 1.3-15.9). Meanwhile, subjects with GC had a higher risk of DILI incidence (OR: 4.3, 95% CI: 0.8-24.4). CONCLUSION: Our study shows that polymorphisms of CYP2E1 and slow acetylator may have role in the DILI incidence.
OBJECTIVE: A polymorphism of CYP2E1 may be directly associated with the development of INH hepatotoxicity. We conducted this study to evaluate the association between polymorphisms of CYP2E1, Isoniazid (INH) concentration and the acetylator status of INH in cases of Indonesian tuberculosispatients with drug-induced liver disease (DILI). METHODS: We conducted our study with a cohort design consisting of 55 Indonesian adult tuberculosis (TB) patients. Acetylating phenotypes were studied in using the metabolic ratio of plasma AcHZ/HZ. DILI was defined using CTCAV version 4.0. The allelic and genotypic frequency distributions of CYP2E1 rs 3813867 were studied using the polymerase chain reaction - amplification refractory mutation system (ARMS) methodology. RESULTS:Patients with an INH concentration of more than 7μg/mL showed a higher risk of developing DILI when compared with patients who showed a therapeutic range of 3-6μg/mL INH (OR: 1.3, 95% CI: 0.2-8.2). Slow acetylators had a higher incidence of DILI when compared with rapid acetylators (OR: 4.6, 95% CI: 1.3-15.9). Meanwhile, subjects with GC had a higher risk of DILI incidence (OR: 4.3, 95% CI: 0.8-24.4). CONCLUSION: Our study shows that polymorphisms of CYP2E1 and slow acetylator may have role in the DILI incidence.