The A/A Genotype of XPO1 rs4430924 Is Associated With Higher Risk of Antituberculosis Drug-Induced Hepatotoxicity in Chinese Patients.

Antituberculosis (anti-TB) drug-induced hepatotoxicity may be related to the excessive reactive oxygen species induced by hepatotoxic metabolites. Antioxidant activity involves the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. The BTB domain and CNC homologue 1 (Bach1) may compete with Nrf2 for binding to transcriptional enhancers. Elimination of Bach1-mediated transcriptional repression depends on nuclear exporter exportin 1 (Xpo1). Thus, Xpo1 may indirectly affect antioxidant activity. The present study aimed to examine the role of tag single-nucleotide polymorphisms in XPO1 in Chinese anti-TB treatment patients. A 1:2 matched case-control study was conducted using 314 anti-TB drug-induced hepatotoxicity cases and 628 controls. After correcting for weight and hepatoprotectant use, conditional logistic regression analysis showed that patients carrying the AA genotype of rs4430924 in XPO1 were at higher risk of anti-TB drug-induced hepatotoxicity than those carrying the GG genotype based on the subgroup of probable cases (adjusted OR, 1.938; 95%CI, 1.035-3.628; P = .039), and marginally significant differences were also found under the recessive model (P = .048) and the additive model (P = .047). Based on this 1:2 matched case-control study, the AA genotype of rs4430924 in XPO1 may be associated with higher risk of anti-TB drug-induced hepatotoxicity in Chinese anti-TB treatment patients. Further studies in larger and more varied populations are required to validate this relationship.