GENE POLYMORPHISM OF ENDOTHELIAL NITRIC OXIDE SYNTHASE IN PATIENTS WITH STABLE ANGINA PECTORIS AND ITS SIGNIFICANCE IN THE MANIFESTATION OF GENOPROTECTIVE PROPERTIES OF MELDONIUM

Introduction: Personalized pharmacotherapy of stable angina pectoris implies an in-depth study of the pharmacogenetic factor when prescribing the recommended drugs in order to increase the effectiveness and safety of their use. The work is devoted to the development of individual approaches to the appointment of meldonium in the complex pharmacotherapy of angina pectoris as a cardiac cytoprotector with endothelioprotective properties, depending on gene polymorphism of endothelial nitric oxide synthase. Research tasks: To study the polymorphism of the endothelial nitric oxide synthase gene eNOS C786T and to evaluate the significance of this factor in the manifestation of the genoprotective properties of meldonium in patients with stable angina pectoris. Methods: A total of 90 patients with stable angina pectoris were examined. DNA was isolated from blood leukocytes from patients. The polymorphism of endothelial nitric oxide synthase eNOS C786T was determined by polymerase chain reaction. By the method of DNA comets according to the method developed by us in in vitro tests, the effect of meldonium on the DNA of blood leukocytes of patients was evaluated. The content of cortisol, cyclic AMP and cyclic GMP in the blood serum of patients, concentration of endothelial and inducible nitric oxide synthases in erythrocytes was determined by the enzyme immunoassay. Results: The presence of gene polymorphisms of eNOS C786T alleles was found. They revealed a more severe clinical condition of patients having pathological genes by eNOS C786T alleles in the form of signs of a decrease in the activity of stress-limiting and increasing activity of stress-realizing systems at the level of humoral regulation and intracellular messengers in connection with the apparent decrease in the enzymatic activity of endothelial nitric oxide synthase. Potential genotoxicity of meldonium was revealed when it was administered to patients with a pathological genotype of endothelial nitric oxide synthase eNOS C786T (CC, CT) and a genoprotective effect when administered to patients with a normal genotype of endothelial nitric oxide synthase eNOS C786T (TT). Conclusion: When prescribing meldonium to patients with stable angina, one should take into account the genetic information on the individual polymorphism of the endothelial nitric oxide synthase gene and give preference to individuals who have the normal genotype of eNOS C786T (TT) in view of the predicted genoprotective effect of the drug. Key words: pharmacogenetics, polymorphism of the gene eNOS C786T, meldonium, genotoxicity, genoprotection, personalized pharmacotherapy.