R Chen1, J Wang1, S-W Tang2, Y Zhang3, X-Z Lv4, S-S Wu1, Z-R Yang1, Y-Y Xia5, D-F Chen1, S-Y Zhan1. 1. Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China. 2. Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China. 3. Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada. 4. Clinical Research Division, Peking University Institute of Mental Health, and Key Laboratory for Mental Health, Ministry of Health, Beijing, China. 5. Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
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.
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.