Impact of nitric oxide synthase 2 gene variant on risk of anti-tuberculosis drug- induced liver injury in the Malaysian population

• Main Authors: Vishala Sivapalan,, Shamsul Mohd Zain,, Jin, Shengnan, Chan, Sze Ling, Liu, Jiajun, Zahurin Mohamed,, Rosmawati Mohamed,
• Format: Article
• Language: English
• Published: Penerbit Universiti Kebangsaan Malaysia 2020
• Online Access: http://journalarticle.ukm.my/14756/1/ARTIKEL%202.pdf; http://journalarticle.ukm.my/14756/; http://www.ukm.my/jsm/malay_journals/jilid49bil2_2020/KandunganJilid49Bil2_2020.html

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.