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Home / The International Journal of Tuberculosis and Lung Disease, Volume 20, Number 6

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

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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.

Keywords: ATDH; genetic susceptibility; pharmacogenetics; tuberculosis

Document Type: Research Article

Affiliations: 1: Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing 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 5: Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China

Publication date: 01 June 2016

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  • The International Journal of Tuberculosis and Lung Disease (IJTLD) is for clinical research and epidemiological studies on lung health, including articles on TB, TB-HIV and respiratory diseases such as COVID-19, asthma, COPD, child lung health and the hazards of tobacco and air pollution. Individuals and institutes can subscribe to the IJTLD online or in print – simply email us at [email protected] for details.

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