NAT2 variants are associated with drug-induced liver injury caused by anti-tuberculosis drugs in Indonesian patients with tuberculosis.

Autor: Yuliwulandari R; Department of Pharmacology, Faculty of Medicine, YARSI University, Jakarta Pusat, Indonesia.; Genomic Medicine Research Group, YARSI Research Institute, YARSI University, Jakarta Pusat, Indonesia., Susilowati RW; Department of Histology, Faculty of Medicine, YARSI University, Jakarta Pusat, Indonesia., Wicaksono BD; Genomic Medicine Research Group, YARSI Research Institute, YARSI University, Jakarta Pusat, Indonesia., Viyati K; Department of Histology, Faculty of Medicine, YARSI University, Jakarta Pusat, Indonesia., Prayuni K; Genomic Medicine Research Group, YARSI Research Institute, YARSI University, Jakarta Pusat, Indonesia., Razari I; Genomic Medicine Research Group, YARSI Research Institute, YARSI University, Jakarta Pusat, Indonesia., Kristin E; Department of Pharmacology and Therapy, Faculty of Medicine, Gadjah Mada University, Yogyakarta, Indonesia., Syafrizal; Pasar Rebo General Hospital, Jakarta Timur, Indonesia., Subagyo; Pasar Rebo General Hospital, Jakarta Timur, Indonesia., Sri Diana E; Pasar Rebo General Hospital, Jakarta Timur, Indonesia., Setiawati S; Pasar Rebo General Hospital, Jakarta Timur, Indonesia., Ariyani A; Pasar Rebo General Hospital, Jakarta Timur, Indonesia., Mahasirimongkol S; Medical Genetics Section, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand., Yanai H; Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan., Mushiroda T; Research Group for Pharmacogenomics, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan., Tokunaga K; Department of Human Genetics, School of International Health, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Jazyk: angličtina
Zdroj: Journal of human genetics [J Hum Genet] 2016 Jun; Vol. 61 (6), pp. 533-7. Date of Electronic Publication: 2016 Feb 25.
DOI: 10.1038/jhg.2016.10
Abstrakt: Drug-induced liver injury (DILI) is the most common adverse drug reaction in the treatment of tuberculosis (TB). Several studies showed that patients with TB and the slow-acetylator phenotype caused by NAT2 variants are highly susceptible to DILI caused by anti-TB drugs, hereafter designated AT-DILI. However, the role of NAT2 variants in AT-DILI has never been assessed for an Indonesian population. We recruited 50 patients with TB and AT-DILI and 191 patients with TB but without AT-DILI; we then used direct DNA sequencing to assess single-nucleotide polymorphisms in the coding region of NAT2. NAT2*6A was significantly associated with susceptibility to AT-DILI (P=7.7 × 10(-4), odds ratio (OR)=4.75 (1.8-12.55)). Moreover, patients with TB and the NAT2-associated slow-acetylator phenotype showed higher risk of AT-DILI than patients with the rapid- or intermediate-acetylator phenotypes (P=1.7 × 10(-4), OR=3.45 (1.79-6.67)). In conclusion, this study confirms the significance of the association between slow-acetylator NAT2 variants and susceptibility to AT-DILI in an Indonesian population.
Databáze: MEDLINE
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