Association of the genotype of the xenobiotic biotransformation enzyme ( GSTM1) in patients with pulmonary tuberculosis with the effectiveness of the intensive phase of chemotherapy

The gene system of enzymes of xenobiotic metabolism plays an important role in the metabolism of many substances entering the human body. According to the available scientific research, a certain amount of information has accumulated on the study of polymorphic variants of genes for xenobiotic biotransformation enzymes in bronchopulmonary pathology, in particular pulmonary tuberculosis. The aim of the study was to identify the relationship between the genotype of the xenobiotic biotransformation enzyme (GSTM1) in patients with pulmonary tuberculosis and the effectiveness of the intensive phase of chemotherapy. Material and methods. The research includes an analysis of modern literature, the development and formulation of goals and objectives of the work, the design of the scientific work carried out, the collection, processing and analysis of the results, the formulation of conclusions and practical recommendations. To solve these tasks, we analyzed the clinical, laboratory and instrumental data of 335 patients with pulmonary tuberculosis aged 18 to 65 years receiving intensive chemotherapy, including 212 patients with newly diagnosed and 123 people with chronic pulmonary tuberculosis. Associations of alleles and genotypes with predisposition to pulmonary tuberculosis were assessed using the odds ratio. Results of the study. The study revealed that in patients with newly diagnosed pulmonary tuberculosis, scarring of the decay cavities is 2,9 times more often associated with the genotype of its GSTM1 gene, while in patients with chronic pulmonary tuberculosis it is 2,4 times more often compared with the DD genotype of the GSTM1 gene (p < 0.001). A decrease in lung tissue infiltration is 5,3 times more often associated with the genotype of its GSTM1 gene in patients with newly diagnosed pulmonary tuberculosis, while in patients with chronic pulmonary tuberculosis it is 1,7 times more often compared with the DD genotype of the GSTM1 gene (p < 0,001). Conclusion. The genotype of GSTM1 gene is an independent predictor of the most favorable course of tuberculosis infection, while the DD genotype of the GSTM1 gene is associated with the most unfavorable course of this infection.

1. Belushkina H. H., Chemezov A. C., Fingers M. A. Genetic studies of multifactorial diseases in the concept of personalized medicine. Profilakticheskaya meditsina= Preventive medicine. 2019; 3: 26–29.

2. Vasilyeva I. A., Belilovsky E. M., Borisov C. E. Morbidity, mortality and prevalence as indicators of the burden of tuberculosis in WHO regions, countries of the world and in the Russian Federation (Part 1). Tuberkulez i bolezni legkikh = Tuberculosis and lung diseases. 2017; 95 (6): 8–21.

3. Nechaeva O. B. Socially significant infectious diseases that pose a biological threat to the Russian population. Tuberkulez i bolezni legkikh= Tuberculosis and lung diseases. 2019; 11: 7–17.

4. Galkin V. B., Sterlikov S. A., Balasanyants G. S. The dynamics of the prevalence of multidrug-resistant tuberculosis. Tuberkulez i bolezni legkikh = Tuberculosis and lung diseases. 2017; 3: 5–11.

5. Sectoral and economic indicators of anti-tuberculosis work in 2016-2017. An analytical review of the main indicators and statistical materials. Moscow: RIO TSNIIOIZ; 2018: 81 p.

6. Putin V. V. Speech at the First WHO Global Ministerial Conference (2017). An electronic resource. URL: https://corp.wtcmoscow.ru/nevvs/vvstuplenie-prezidenta-rossii-na-pervov-globalnov-ministerskov-konferentsii-voz (accessed: 02.05.2025).

7. Sinitsyn M. B., Kalinina M. B., Belilovsky E. M. Tuberculosis treatment in modern conditions. Terapevticheskiy arkhiv = Therapeutic Archive. 2020; 92 (8): 86–94.

8. Stepanova N. A., Streltsova E. N., Galimzyanov H. M., Kantemirova B. I. Polymorphism of N-acetylation (NAT-2) genes and clinical and radiological features of the course of pulmonary tuberculosis. Tuberku-lez – globalnaya katastrofa chelovechestva = Tuberculosis – a global catastrophe of mankind. Rostov-on-Don; 2015: 45–47

9. Virina E. B., Kantemirova B. I. Genetic predictors of the formation of undesirable side effects of antituberculosis drugs: focus on glutathione transferase polymorphism. Novaya nauka: ot idei k rezultatu = New science: from idea to result. 2015; 2: 29–31.

10. Kostyuk C. A. Xenobiotic biotransformation system: detoxification genes. Meditsinskie novosti = Medical news. 2020; 11: 12–16.

11. Churnosov M. I., Polyakova I. S., Pakhomov S. P., Orlova V. S. Molecular and genetic mechanisms of biotransformation of xenobiotics. Nauchnye vedomosti Belgorodskogo universiteta = Scientific bulletin of Belgorod University. 2011; 16: 223–228.

12. Demidchik Yu. E., Kostyuk C. A., Tretyak I. Y. Mekhanizmy kletochnoy khimiorezistentnosti pri rake molochnoy zhelezy = Mechanisms of cellular chemoresistance in breast cancer. Minsk; 2016: 152 p.

13. Nevzorov B. A., Panchenko E. A., Isaeva M. P. Deletion polymorphism of glutathione transferase T1 and Ml genes in patients with myocardial infarction and metabolic syndrome. Kardiovaskulyarnaya terapiya i profilaktika = Cardiovascular therapy and prevention. 2014; 3: 47–52.

14. Knizhnikova E. B., Evseeva G. P., Nagovitsyna E. B. The role of genes of biotransformation of xenobiotics of the glutathione-S-transferase family (GSTS) in the formation of predisposition to diseases of the bronchopulmonary system. Byulleten fiziologii i patologii dykhaniya = Bulletin of Physiology and Pathology of Respiration. 2020; 75: 115–125.

15. Korytina G. F., Akhmadishina L. Z., Zagidullin Sh. Z., Viktorova T. V. Analysis of genetic factors involved in the development of chronic obstructive pulmonary disease: assessment of the contribution of xenobiotic biotransformation and antioxidant protection genes. Pulmonologiya = Pulmonology. 2013; 1: 25–31.

16. Kukes V. G. Klinicheskaya farmakogenetika= Clinical pharmacogenetics. Moscow; 2007: 248 p.

17. Wu S., Wang Y. J., Tang X., Wang Y., Wu J., Ji G., Zhang M., Chen G., Liu Q., Sandford A. J., He J. Q. Genetic Polymorphisms of Glutathione S-Transferase P1 (GSTP1) and the Incidence of Anti-Tuberculosis DrugInduced Hepatotoxicity. PLoS One. 2016 Jun 9; 11 (6): e0157478. doi: 10.1371/journal.pone.0157478.

18. Alymenko M. A., Valiev R. Sh., Polonikov A. V., Golubeva T.N., Vasilevskay A.P., Miroshnik E.V. Association of polymorphic gene variants of xenobiotic biotransformation enzymes with susceptibility to the incidence of pulmonary tuberculosis. Tuberkulez i bolezni legkikh = Tuberculosis and lung diseases. 2022; 100 (6): 17–22.

19. Alymenko M. A., Valiev R.Sh., Valiev H. P., Polonikov A.V, Tragira I.N., Sheenkov N.V. Association of polymorphic gene variants of xenobiotic and cytokine biotransformation enzymes with the destruction of lung tissue in tuberculosis patients. Tuberkulez i bolezni legkikh = Tuberculosis and lung diseases. 2022; 100 (8): 25–30.