and Genetic Polymorphisms and Their Association with Antituberculosis Drug-induced Liver Injury

Antituberculosis (anti-TB) drugs are the most common cause of drug-induced liver injury (DILI). There are numerous studies revealing the associations between the polymorphisms of pharmacogenes and the risk of anti-TB DILI (ATDILI). In the present study, relevant studies regarding the pharmacogenes associated with ATDILI were systematically searched in PubMed and Scopus. A total of 24 genes associated with ATDILI were reported on and the top five reported genes in terms of frequency were revealed to be N-acetyltransferase 2, cytochrome P450 family 2 subfamily E member 1, glutathione S-transferases [glutathione S-transferase mu 1 () and glutathione S-transferase theta 1 ()] and solute carrier organic anion transporter family member 1B1. As ATDILI may be the result of direct and indirect interactions, the encoded proteins were further analysed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) to observe the protein-protein interactions and the associations amongst these proteins. The results suggested that only and were central proteins associated with all the other analysed proteins. Therefore, the association between or and the risk of developing ATDILI were further analysed. The results revealed that a deletion genotype was significantly associated with risk of ATDILI [odds ratio (OR), 1.28; 95% confidence interval (CI), 1.08-1.51; P=0.004], whereas the deletion genotype and dual-deletion genotype were not significantly associated with risk of ATDILI. Subgroup analysis based on ethnicity was performed and the results demonstrated a significant association between and ATDILI in South Asian individuals (OR, 1.48; 95% CI, 1.12-1.95; P=0.005), which has not been reported previously, to the best of our knowledge. In conclusion, was associated with ATDILI in South Asian individuals.