Effect of Genetic Polymorphism of the Enzyme Genes Responsible for Biotransformation of Antituberculous Drug on the Risk of Hepatotoxic Reaction in Patients with Tuberculosis

Purpose ofthe study: To increase the effectiveness and safety of chemotherapy for tuberculosis patients based on knowledge ofpatient's genotypic characteristics through molecular genetic methods of research.Methods: A total of 95 people aged 12 to 50 took part in the study. In the treatment regimen, the patients of the main group were treated with isoniazid, pyrazinamide and rifampicin. Adverse hepatotoxic reactions in the form of clinical manifestations and (or) increase in the level of ALT and AST were observed in 23 patients. Hepatoprotective therapy with drugs Carsil, Phosphogliv was received by all patients.To conduct laboratory tests, genomic DNA was isolated from whole blood and the polymerase chain reaction was performed in real time. In the study group the presence of genotypes belonging to the genes listed below was considered as possible predictors of hepatotoxicity: rs1801279, rs1799931, rs1799930, rs1799929, rs1801280, rs1208, rs1041983, rs1045642, rs74837985.To predict the development of hepatotoxicity with the use of antituberculosis drugs, the method of logistic regression analysis was used depending on the presence or absence of specific genotypes in the genome of the examinee. Results: As a result of the logistic regression analysis two statistically significant models were obtained. The first model reflects the association of the antituberculous-drugs hepatotoxicity with the AA genotype of the rs1799931 gene and the AA and AG (allele A) genotypes of the rs1799930 gene. The second model reflects the connection of the antituberculousdrugs hepatotoxicity manifestation with the TT and CT (allele T) genotypes of the rs1041983 gene. Conclusions: The presence of the AA genotype of the rs1799931 gene and the AA and AG (allele A) genotypes of the rs1799930 gene as well as the presence of the TT or CT (allele T) genotype of the rs1041983 gene, which determine the activity of the NAT2 enzyme, significantly increases the risk of hepatotoxicity during therapy with antituberculous drugs in patients with pulmonary tuberculosis.

tuberculosis, gene polymorphism, hepatotoxic reactions, antituberculous drugs

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