RS4673 and pon1 level in blood plasma - new prospects in prediction and early diagnostics of anthracycline-mediated cardiotoxicity.

The purpose of this study was to research the effectiveness of molecular genetic tests based on the determination of the rs4673 CYBA polymorphism (c.242C>T) and the level of paraoxonase 1 (PON1) in the blood plasma of patients with breast cancer (BC) for predicting and diagnosing anthracycline-mediated cardiotoxicity (AMC). The genotyping of rs4673 CYBA (c.242C>T) and the study of the PON1 level in the blood plasma of 280 patients of the Caucasian type with a histologically verified diagnosis of breast cancer, who received complex treatment on the basis of the National Medical Research Center of Oncology, were carried out. Based on the results of observation for at least 8 months, two groups were identified: group 1 (257 people) without diagnosed cardiovascular changes; group 2 (23 people) - patients with subacute and early chronic AMC. It was found that carriers of the rs4673 polymorphism increase the likelihood of developing AMC by 6.8 times (p = 0.001). In the blood plasma of both groups of patients, an increase in the level of PON1 was described after the fourth course compared to the initial level (group 1 - p = 0.036, group 2 - p = 0.048). The level of the studied enzyme was higher in the blood plasma of patients with diagnosed AMC compared with patients without cardiovascular complications (before chemotherapy - p = 0.001, after the fourth course - p = 0.023). The test based on the measurement of the concentration of PON1 in the blood plasma of patients after the fourth course of chemotherapy was distinguished by high quality metrics: sensitivity - 100%, specificity - 70.8%, area under the ROC-curve (AUC) - 0.825 with a threshold level of PON1 equal to 2, 9 ng/µL. The presence of the T/T genotype caused a high level of PON1 in the blood plasma after the fourth course of chemotherapy (p = 0.012). The results of our work are of undoubted practical importance, since they allow us to obtain data on the prognosis and diagnosis of a patient in a short time, which can later be verified using clinical and instrumental methods.

[Concentration of proinflammatory cytokines, peroxiredoxin-1 and glutathione peroxidase activity in the blood plasma of patients with coronary artery disease undergoing coronary artery bypass grafting].

76 patients with coronary heart disease (who had undergone coronary artery bypass grafting) were examined to investigate the role of pro-inflammatory cytokines and enzymes involved in redox regulation, in the mechanisms of development of systemic inflammatory response syndrome. Patients were divided into 2 groups: 1st - patients with coronary heart disease, who as a result of clinical trials has not been set postpericardiotomy syndrome; 2nd - patients with coronary heart disease who have been diagnosed postpericardiotomy syndrome. The blood plasma of both groups indicated intensification of production of interleukin-6, intrleukin-8, as well as - an imbalance in the peroxiredoxin-1 and glutathione peroxidase. These changes by patients with postpericardiotomy syndrome are observed at the earliest time and differed depth of expression. The results of this work confirm the high potential of the investigated indicators for prevention and monitoring postpericardiotomy syndrome development.

[PROINFLAMMATORY CYTOKINE GENE POLYMORPHISMS AND THE PLASMA AND SYNOVIAL FLUID LEVELS OF CYTOKINES IN PATIENTS WITH POST-TRAUMATIC KNEE OSTEOARTHRITIS].

Post-traumatic knee osteoarthritis patients (n=117) and healthy people (n=94) were investigated to determine the genotypic and allelic frequency distribution of polymorphic loci Т-31С, С+3953Т IL-1ß and G-308A TNF-α. The plasma and synovial fluid levels of proinflammatory cytokines IL-1ß and TNF-α were measured in 31 patients. The research demonstrated that the blood and synovial fluid levels of IL-1ß but not TNF-α were increased in patients with post-traumatic knee osteoarthritis. Also, the linkage between TNF-α level and polymorphic locus G-308A TNF-α was shown: the presence of allele -308А was associated with decreased TNF-α level. We demonstrated that polymorphic loci Т-31С, С+3953Т IL-1ß and G-308A TNF-α do not predict the higher risk of post-traumatic knee osteoarthritis development in Russian population of Rostov-on-Don region.