title: NAT2 variants are associated with drug-induced liver injury caused by anti-tuberculosis drugs in Indonesian patients with tuberculosis.
abstract: 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.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, YARSI University, Jakarta Pusat, Indonesia.|Genomic Medicine Research Group, YARSI Research Institute, YARSI University, Jakarta Pusat, Indonesia.
authors.forename: Rika
authors.initials: R
authors.lastname: Yuliwulandari
authors.affiliation: Department of Histology, Faculty of Medicine, YARSI University, Jakarta Pusat, Indonesia.
authors.forename: Retno Wilujeng
authors.initials: RW
authors.lastname: Susilowati
authors.affiliation: Genomic Medicine Research Group, YARSI Research Institute, YARSI University, Jakarta Pusat, Indonesia.
authors.forename: Britanto Dani
authors.initials: BD
authors.lastname: Wicaksono
authors.affiliation: Department of Histology, Faculty of Medicine, YARSI University, Jakarta Pusat, Indonesia.
authors.forename: Kencono
authors.initials: K
authors.lastname: Viyati
authors.affiliation: Genomic Medicine Research Group, YARSI Research Institute, YARSI University, Jakarta Pusat, Indonesia.
authors.forename: Kinasih
authors.initials: K
authors.lastname: Prayuni
authors.affiliation: Genomic Medicine Research Group, YARSI Research Institute, YARSI University, Jakarta Pusat, Indonesia.
authors.forename: Intan
authors.initials: I
authors.lastname: Razari
authors.affiliation: Department of Pharmacology and Therapy, Faculty of Medicine, Gadjah Mada University, Yogyakarta, Indonesia.
authors.forename: Erna
authors.initials: E
authors.lastname: Kristin
authors.affiliation: Pasar Rebo General Hospital, Jakarta Timur, Indonesia.
authors.lastname: Syafrizal
authors.affiliation: Pasar Rebo General Hospital, Jakarta Timur, Indonesia.
authors.lastname: Subagyo
authors.affiliation: Pasar Rebo General Hospital, Jakarta Timur, Indonesia.
authors.forename: Eva
authors.initials: E
authors.lastname: Sri Diana
authors.affiliation: Pasar Rebo General Hospital, Jakarta Timur, Indonesia.
authors.forename: Suci
authors.initials: S
authors.lastname: Setiawati
authors.affiliation: Pasar Rebo General Hospital, Jakarta Timur, Indonesia.
authors.forename: Aziza
authors.initials: A
authors.lastname: Ariyani
authors.affiliation: Medical Genetics Section, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand.
authors.forename: Surakameth
authors.initials: S
authors.lastname: Mahasirimongkol
authors.affiliation: Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Yanai
authors.affiliation: Research Group for Pharmacogenomics, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.
authors.forename: Taisei
authors.initials: T
authors.lastname: Mushiroda
authors.affiliation: Department of Human Genetics, School of International Health, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tokunaga
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D000995:Antitubercular Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D016022:Case-Control Studies; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis / Q000209:etiology*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007214:Indonesia; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D014376:Tuberculosis / Q000150:complications* / Q000188:drug therapy / Q000235:genetics*; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human