Impact of Nitric Oxide Synthase 2 Gene Variant on Risk of Anti-Tuberculosis Drug- Induced Liver Injury in the Malaysian Population
Document Type
Article
Publication Date
1-1-2020
Abstract
Liver injury is a great threat associated with anti-tuberculosis (anti-TB) medication. Genetic variations in genes encoding drug-metabolising enzymes further enhance this threat. We aimed to explore genetic contributions by evaluating the impact of single nucleotide polymorphisms (SNPs) within the anti-tuberculosis (AT) metabolism pathway genes and within their respective chromosomes on anti-tuberculosis drug-induced liver injury (AT-DILI). Patients (n= 90) were recruited and 170 SNPs were genotyped using Illumina array and validated using Sanger Sequencing. The well-studied N-acetyltransferase 2 (NAT2*6) rs1799930 and cytochrome P450 2E1 (CYP2E1) C1/C1 were not significantly associated with AT-DILI in our cohort but nitric oxide synthase (NOS2A) rs11080344-C was found to be significantly higher in the cases than the controls (OR 2.73, 95% CI 1.12-6.64, P= 0.027). Association studies on all other SNPs within the anti-tuberculosis metabolism pathway genes and within their respective chromosomes also found no significant report. Our study suggests that genetic variation in NOS2A could influence the occurrence of AT-DILI. © 2020 Penerbit Universiti Kebangsaan Malaysia. All rights reserved.
Keywords
Adverse effect, Genetic variations, Liver injury, Nitric oxide, Tuberculosis
Divisions
fac_med
Funders
High Impact Research Grants, University Malaya (UM.C/625/1/HIR/187, J-20001-738610),High Impact Research Grants, Ministry of Higher Education, Malaysia (HIR MOHE E000049-20001)
Publication Title
Sains Malaysiana
Volume
49
Issue
2
Publisher
Penerbit Universiti Kebangsaan Malaysia