РОЛЬ ПОЛИМОРФНЫХ ВАРИАНТОВ ГЕНОВ NO-СИНТАЗЫ, РЕЦЕПТОРА ЭНДОТЕЛИНА-1 И NADPH-ОКСИДАЗЫ ПРИ РАЗВИТИИ СЕРДЕЧНОЙ НЕДОСТАТОЧНОСТИ, ИНДУЦИРОВАННОЙ КАРДИОТОКСИЧНОСТЬЮ ХИМИОТЕРАПИИ

Aim.  To study the clinical and genetic aspects of the influence of polymorphic variants of the genes of endothelial NO-synthase (NOS3), the receptor of endothelin-1 type A (EDNRA) and NADPH-oxidase on the development of cardiotoxic remodeling of the left ventricle and heart failure during anthracycline-based regimens for patients with breast cancer. Methods.  176 women with breast cancer receiving anthracycline antibiotics as part of multiple drug chemotherapy regimens were examined. According to the results of the examination, 12 months after the end of multiple drug chemotherapy, all the patients with the main disease in remission were divided into 2 groups: patients with cardiac remodeling caused by cardiotoxicity (Group 1 = 52) and those with preserved heart function (Group 2 = 124). All patients underwent echocardiographic assessment before chemotherapy, during the treatment regimen with anthracyclines and after the therapy. Genetic material (buccal cells) was collected from all patients for the subsequent typing of alleles of genes NOS3 (rs1799983), EDNRA (rs5335) and NADPH-oxidase (rs4673). Results.  Analysis of echocardiographic parameters in patients 12 months after the completion of multiple drug chemotherapy in comparison with those before treatment showed a statistically significant difference between end-systolic and end-diastolic dimensions, as well as a significant reduction in the left ventricular ejection fraction in the group of women who developed cardiotoxicity with anthracycline cardiotoxicity. An association between the development of cardiotoxic lesions with the presence of mutant allele of NOS3 rs1799983 and NADPH-oxidase rs4673 genes has been determined. The presence of the T/T genotype of the NOS3 rs1799983 gene was associated with myocardial damage during multiple drug chemotherapy, along with the T/T genotype of the NADPHoxidase gene rs4673. Importantly, the genotype G/G of the gene NOS3 rs1799983 was more frequently determined in Group 2, suggesting its protective effect against cardiotoxic myocardial damage. Conclusion.  The development of the strategy aimed at preventing or reducing the risk of cardiovascular complications in the treatment of cancer is a crucial problem. Genetic typing is an effective measure to predict the increased risk of cardiotoxic effects of anthracyclines.