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Original Research

Is anti-tuberculosis drug-induced hepatotoxicity due to a change in pharmacokinetics caused by alterations in antioxidant gene expression and polymorphisms in the NFE2L2 gene? 

Guiyi Ji, Weiwei Huang, and Jianqing He

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Volume 58 (2020) p. 67 - 73

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 58 – No. 2/2019 (67-73)

Is anti-tuberculosis drug-induced hepatotoxicity due to a change in pharmacokinetics caused by alterations in antioxidant gene expression and polymorphisms in the NFE2L2 gene? 

Guiyi Ji¹#²*, Weiwei Huang¹*, and Jianqing He¹

¹Department of Respiratory and Critical Care Medicine, and ²Health Management Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
Objective: Anti-tuberculosis drug-induced hepatotoxicity (ATDH) is a major adverse reaction of tuberculosis (TB) therapy. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a master transcription factor encoded by the NFE2L2 gene. Nrf2 regulates the expression of antioxidant genes which affect the kinetics of drugs and other xenobiotics, and plays a key role in the regulation of cellular redox status. We investigated the potential association of NFE2L2 single-nucleotide polymorphisms (SNPs) with ATDH.
Materials and methods: 280 newly diagnosed TB patients were recruited in this prospective study and were followed up for 3 months after initiating anti-TB therapy. Five tagSNPs (rs2001350, rs6726395, rs1962142, rs13001694, and rs2364723) were selected based on a Han Chinese panel in the International HapMap database with a minor allele frequency < 5% and an r² threshold of 0.8.
Results: Of the 280 subjects recruited in this research, there were 24 patients diagnosed with ATDH, 223 subjects without ATDH, and 33 individuals excluded during the follow-up. After adjusting for confounding factors including sex, age, smoking status, and body mass index, there was no statistically significant difference.
Conclusion: Our results suggest that NFE2L2 variants may not contribute to the pathogenesis of ATDH in a Chinese population. Further large sample studies and various population studies are needed to fully explore the association between ATDH and NFE2L2 polymorphism.

*Guiyi Ji and Weiwei Huang contributed equally.Correspondence to:
 Jianqing He, MD
Department of Respiratory and Critical Care Medicine
West China Hospital, Sichuan University
Chengdu 610041, Sichuan, China
Email: [email protected]

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