VARIABILITY OF THE GENES OF NATRIURETIC PEPTIDES AND ANTIOXIDANT PROTECTION IN PATIENTS WITH MYOCARDIAL INFARCTION
Authors:   Research Institute of Complex Problems of Cardiovascular Diseases, Ministry of Science and Higher Education of the Russian Federation, Kemerovo Russian Federation, Khryachkova O. N. , Khutornaya Maria V. ,   Research Institute of Complex Problems of Cardiovascular Diseases, Ministry of Science and Higher Education of the Russian Federation, Kemerovo Russian Federation, Sinitskaya A. V. ,   Research Institute of Complex Problems of Cardiovascular Diseases, Ministry of Science and Higher Education of the Russian Federation, Kemerovo Russian Federation, Poddubnyak Alyona O ,   Research Institute of Complex Problems of Cardiovascular Diseases, Ministry of Science and Higher Education of the Russian Federation, Kemerovo Russian Federation, Ponasenko A V ,   Research Institute of Complex Problems of Cardiovascular Diseases, Ministry of Science and Higher Education of the Russian Federation, Kemerovo Russian Federation
Published: October 2023

Introduction. Cardiovascular diseases (CVD) continue to be the subject of scientific research in relation to molecular genetic predictors of their development. It has been proven that diseases of the cardiovascular continuum have a multifactorial nature with a significant genetic component, including the hereditary risk of myocardial infarction (MI). CVDs are characterized by a complex genetic structure with diverse combinations of single nucleotide polymorphic variants (SNVs). A promising task is to study the relationship of SNV adaptogenesis genes: inflammatory response, myocardial and endothelial dysfunction with developed MI in the Siberian population. Purpose: to reveal the relationship between SNV genes of natriuretic peptides and the antioxidant defense system with the development of myocardial infarction. Materials and methods. The material for the study was genomic DNA isolated from the peripheral blood of patients (n=146, 38 women and 108 men) admitted for treatment at the Kuzbass Clinical Cardiological Dispensary, Kemerovo, with a diagnosis of MI. The control group is represented by a population sample of residents of the city of Kemerovo (n=300, 190 women and 110 men). 20 polymorphic variants of 7 natriuritic peptide genes (NPPA, NPPA-AS1, NPPB, NPPC, NPR1, NPR2, NPR3) and 5 genes of the antioxidant defense system (SOD2, NCF4, CBR1, CBR3, CAT) were selected for the study. Genotyping of selected polymorphic variants was performed by real-time PCR using TaqMan technology. Statistical data analysis was carried out using GraphPad Prism 8 and SNPstats software. Results. Protective associations of allelic variants of the CBR1 rs9024 genes (OR=0.21 (95% CI 0.13-0.34); p=0.0001) and CBR3 (OR=0.44 (95% CI 0.28-0) .69); p=0.001) regardless of gender according to the dominant model of inheritance. When separating patients by gender, it was found that in men, the rs9024 CBR1 allele A (OR=0.20 (95% CI 0.11-0.36); p<0.0001) and the rs1056892 CBR3 allele A (OR=0, 51 (95% CI 0.28-0.91); p=0.022) have a protective effect in the development of MI according to the dominant model of inheritance. Allele T rs2236289 (OR=1.93 (95% CI 1.04-3.58); p=0.035) and allele A rs7034957 (OR=1.88 (95% CI 1.03-3.45); p =0.038) of the NPR2 gene are associated with a risk effect on the development of myocardial infarction in men according to the dominant model of inheritance. In women, rare alleles of the polymorphic loci rs13288085 (OR=0.25 (95% CI 0.08-0.73); p=0.0034) and rs7034957 (OR=0.30 (95% CI 0.11-0, 79); p=0.007) of the NPR2 gene, rs9024 (OR=0.21 (95% CI 0.09-0.47); p=0.00001) of CBR1, as well as rs1056892 (OR=0.31 (95% CI 0.15-0.64); p=0.0014) CBR3 are characterized by a protective effect on the development of MI according to the dominant model of inheritance. Conclusion. It has been shown that polymorphism of genes for natriuretic peptides and antioxidant protection may have a risky and protective effect in relation to predisposition to the development of MI. The obtained preliminary results indicate the need for further studies of the identified SNV genes of adaptogenesis in relation to the severity of MI and the risk of recurrent cardiovascular events in the long-term period after MI.