The association between BACH1 polymorphisms and anti-tuberculosis drug-induced hepatotoxicity in a Chinese cohort

Anti-tuberculosis drug-induced hepatotoxicity (ATDH) is related to hepatotoxic intermediaries, which are detoxified by glutathione S-transferases (GSTs). GSTM1 and GSTT1 are regulated by nuclear factor erythroid 2-related factor 2 (Nrf2) signalling pathway, and the BTB domain and CNC homologue 1 (Bach1) could compete with Nrf2 for binding to the DNA. Thus, bach1 may indirectly affect GSTs expression. The present study aimed to examine the role of tagSNPs in BACH1 in a Chinese population-based cohort.

A nested case-control study was conducted. Each ATDH case was matched with two controls by age, gender, treatment history, etc. Seven tagSNPs were detected and analysed. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using a conditional logistic regression model.

A total of 290 ATDH cases and 580 controls were included in the present study. Patients carrying GG genotype of rs372883 were at a lower risk of ATDH than with AA genotype (OR = 0.553, 95%CI: 0.357-0.857, P = .008), and significant differences were also found under recessive model (P = .021) and additive model (P = .009). Similar results were also found in the polymorphism of rs1153285 (AA vs. GG, OR = 0.574, 95%CI: 0.360-0.914, P = .019), and under its recessive model (P = .033) and additive model (P = .026). Two haplotypes of A-G-T and C-T-G were identified to be associated with ATDH development. Further subgroup analysis also suggested significant association between BACH1 polymorphisms and ATDH among certain and probable hepatotoxicity cases.

This is the first study to explore the relationship between tagSNPs of BACH1 and ATDH in a Chinese cohort. Based on this cohort, genetic polymorphisms of BACH1 may be associated with susceptibility to ATDH in the Chinese population.