CLINICAL AND GENETIC ASSOCIATIONS OF POLYMORPHIC ALLELES OF THE CYP3A4 GENE IN DRUG-RESISTANT PULMONARY TB PATIENTS

The article represents the results of our study of associations between polymorphic gene variants of the CYP3А4 cytochrome – *1B (rs2740574) and *1G (rs2242480) – and effectiveness and safety of chemotherapy of 115 drug-resistant pulmonary TB patients. We established that patients with polymorphic variants of the CYP3A4 gene – *1B (rs2740574) and *1G (rs2242480) – more commonly demonstrated sputum conversion under bedaquiline-containing chemotherapy, including patients with multi-drug resistance (MDR). However, these patients more commonly developed hemato-, hepato and cardiotoxic adverse drug reactions. The obtained results do not exclude the association between the above-mentioned polymorphic alleles *1G(rs2242480) and *1B (rs2740574) of the CYP3A4 gene and slow phenotypic bedaquiline metabolism.