Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0186200
Title: Association and clinical utility of NAT2 in the prediction of isoniazid-induced liver injury in Singaporean patients
Authors: Chan, Sze Ling 
Chua, Angeline Poh Gek
Aminkeng, Folefac 
Chee, Cynthia Bin Eng
Jin, Shengnan
Loh, Marie 
Gan, Suay Hong
Wang, Yee Tang 
Brunham, Liam R 
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
DRUG-INDUCED HEPATOTOXICITY
N-ACETYLTRANSFERASE 2
CYTOCHROME-P450 2E1 GENOTYPE
S-TRANSFERASE M1
GENETIC POLYMORPHISMS
CYP2E1 POLYMORPHISMS
SUSCEPTIBILITY
RISK
VARIANTS
TUBERCULOSIS
Issue Date: 16-Oct-2017
Publisher: PUBLIC LIBRARY SCIENCE
Citation: Chan, Sze Ling, Chua, Angeline Poh Gek, Aminkeng, Folefac, Chee, Cynthia Bin Eng, Jin, Shengnan, Loh, Marie, Gan, Suay Hong, Wang, Yee Tang, Brunham, Liam R (2017-10-16). Association and clinical utility of NAT2 in the prediction of isoniazid-induced liver injury in Singaporean patients. PLOS ONE 12 (10). ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0186200
Abstract: Background and aims: Isoniazid (INH) is part of the first-line-therapy for tuberculosis (TB) but can cause drug-induced liver injury (DILI). Several candidate single nucleotide polymorphisms (SNPs) have been previously identified but the clinical utility of these SNPs in the prediction of INH-DILI remains uncertain. The aim of this study was to assess the association between selected candidate SNPs and the risk of INH-DILI and to assess the clinical validity of associated variants in a Singaporean population. Methods: This was a case-control study where 24 INH-DILI cases and 79 controls were recruited from the TB control unit in a tertiary hospital. Logistic regression was used to test for the association between candidate SNPs and INH-DILI. NAT2 acetylator status was inferred from genotypes and tested for association with INH-DILI. Finally, clinical validity measures were estimated for significant variants. Results: Two SNPs in NAT2 (rs1041983 and rs1495741) and NAT2 slow acetylators (SA) were significantly associated with INH-DILI (OR (95% CI) = 13.86 (4.30–44.70), 0.10 (0.03–0.33) and 9.98 (3.32–33.80), respectively). Based on an INH-DILI prevalence of 10%, the sensitivity, specificity, positive and negative predictive values of NAT2 SA were 75%, 78%, 28% and 97%, respectively. The population attributable fraction (PAF) and number needed to test (NNT) for NAT2 SA were estimated to be 0.67 and 4.08, respectively. A model with clinical and NAT2 acetylator status provided significantly better prediction for INH-DILI than a clinical model alone (area under receiver operating characteristic curve = 0.863 vs. 0.766, respectively, p = 0.027). Conclusions: We show the association between NAT2 SA and INH-DILI in a Singaporean population and demonstrated its clinical utility in the prediction of INH-DILI.
Source Title: PLOS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/235057
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0186200
Appears in Collections:Elements
Staff Publications

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
Association and clinical utility of NAT2 in the prediction of isoniazid-induced liver injury in Singaporean patients.pdf1.87 MBAdobe PDF

OPEN

PublishedView/Download

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.