CYP7A1, BAAT and UGT1A1 polymorphisms and susceptibility to anti-tuberculosis drug-induced hepatotoxicity.

ABSTRACT

SETTING: Evidence indicates that the polymorphisms in genes involved in bile acid metabolism may play an important role in the development of anti-tuberculosis drug-induced hepatotoxicity (ATDH) in tuberculosis (TB) patients treated with anti-tuberculosis drugs. OBJECTIVE: To investigate the association between genetic variants of CYP7A1, BAAT and UGT1A1 and the risk of ATDH in a Chinese cohort. DESIGN: In this nested case-control study, 89 TB patients with ATDH and 356 matched ATDH-free TB patients constituted cases and controls, respectively. Genetic polymorphisms of CYP7A1, BAAT and UGT1A1 were determined using the TaqMan single-nucleotide polymorphism genotyping assay. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using a conditional logistic regression model. RESULTS: Significant differences were found in genotype distributions of rs1457043 in CYP7A1 between patients with and those without ATDH (P = 0.014). Genotype and haplotype analysis showed that patients carrying an AG genotype of rs1457043 and G-C or G-A haplotypes of rs1457043-rs8192870 in CYP7A1 were at a higher risk of ATDH than those with GG genotype and A-C haplotype, with ORs of respectively 2.05 (95%CI 1.18-3.15) and 2.40 (95%CI 1.62-3.57). CONCLUSION: Genetic polymorphisms of CYP7A1 may be associated with susceptibility to ATDH in the Chinese population.