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

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 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 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 r 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 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 polymorphism.