Objective: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
Keywords: BACH1; Drug-induced hepatotoxicity; Polymorphisms; Tuberculosis.
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