Int. Journal of Clinical Pharmacology and Therapeutics, Volume 58 (2020) - February (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*, Jianqing He1
1 Department of Respiratory and Critical Care Medicine, and 2 Health Management Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China

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DOI 10.5414/CP202599

Abstract

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.

Author Details

Authors

Departments

  • 1 Department of Respiratory and Critical Care Medicine, and
  • 2 Health Management Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China

Address


Jianqing He, MD
Department of Respiratory and Critical Care Medicine
West China Hospital, Sichuan University
Chengdu 610041, Sichuan, China
Email: [email protected]

Citation

Ji G, Huang W, He J.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?
. Int J Clin Pharmacol Ther. 2020; 58: 67-73. doi: 10.5414/CP202599. Pubmed: https://www.ncbi.nlm.nih.gov/pubmed/31670652; PMID: 31670652.

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