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Aim. To identify predictors of heart failure in patients with dilated cardiomyopathy (DCM) and ischemic myocardial dilatation (IMD).Material and methods. In total, we examined 221 patients with cardiomyopathies: DCM and IMD. The mean age of the patients was 55,30±9,69 years (minimum — 20 years, maximum — 77 years). From the total number of patients, a group of patients with DCM (idiopathic origin) (group 1) was identified in the amount of 111 people, of which 99 were men (89,2%) and 12 women (10,8%). The mean age of patients with DCM was 51,73±9,74 years, for men — 51,00±8,96 years, for women — 57,75±3,71 years. The median age in DCM patients was 53,00 [48,00; 58,00], for men — 53,00 [46,00; 57,00], in women — 59,50 [49,00; 68,75]. Patients with IMD (ischemic origin) consisted of 110 people (group 2), of which 100 were men (91,5%) and 10 women (8,5%). The mean age of patients with IMD was 58,68±8,38 years, for men — 58,29±8,46 years, for women — 62,90±6,29 years. The median age in patients with IMD was 58,00 [53,50; 63,50], in men — 58,00 [52,00; 63,00], in women — 61,50 [59,25; 66,00]. Biological material (venous blood) was taken from all patients for molecular genetic analysis. To isolate the DNA structure, the phenol-chloroform extraction was used. Using the polymerase chain reaction, genotyping of gene polymorphisms was carried out, followed by analysis of restriction fragment length polymorphisms.Results. To assess the left ventricular systolic function, the ejection fraction was assessed. Heart failure and its severity are most often associated with a decrease in left ventricular (LV) systolic function. In our study, in the group of patients with DCM, the mean LV ejection fraction (EF) was 25,105±6,76, while in IMD group — 20,255±4,49 (p=0,0001). This confirms that these two groups have severe heart failure associated with impaired LV systolic function — a decrease in EF

The most important task in providing care to patients with myocardial infarction is maintaining myocardial contractility. The article discusses issues related to the influence of genetic characteristics of patients on the repair of infarcted myocardium, the remodeling process, and restoration of left ventricular systolic and diastolic function. One approach to improving the predictive ability of genetic testing is to combine information about many nucleotide sequence variants into a single risk score, often called a polygenic risk score. The article examines recent publications on the creation and use of polygenic risk scores. The use of genetic methods during examination, further consideration of the individual characteristics of each patient when choosing therapy and prescribing a course of rehabilitation will allow for an individual approach to each patient, which in turn should have a positive impact on the disease prognosis.

Aim. To study of the relationship between gene polymorphisms (FGA, ITGA2, PAI1) and pulmonary embolism (PE).Material and methods. We examined 120 patients with pulmonary embolism, who made up the main group (mean age, 63,22±3,16 years). There were 66 men (mean age, 60,24±3,17 years) and 54 women (mean age, 6,19±3,67 years). The control group consisted of 200 people (mean age, 64,92±3,50 years). The DNA Bank of the Research Institute of Internal and Preventive Medicine was formed during a series of population screenings. All patients signed written informed consent to participate in the molecular genetic study. The work involved the calculation of the following output data: standard deviation; mean square; Pearson chi-squared test; likelihood ratio; Fisher's exact test and linear relationship.Results. The probability of PE among women carriers of ID genotype of FGA gene rs35496957 polymorphism in the group with PE is 2,08 times higher than that in the control group (95% confidence interval (CI), 1,06-4,09; p=0,32); among women carriers of the TT genotype of ITGA2 gene rs1126643 polymorphism in the group with PE — 3,08 times compared to the control group (95% CI, 1,36-6,97; p=0,006).Conclusion. The study of genetic factors in the development of pulmonary embolism (FGA, ITGA2, PAI-1) is necessary to create a personalized approach to patient management at all stages.

Aim. To evaluate the association of the nucleotide sequence variant rs1799752 (I/D) of the angiotensin-converting enzyme (ACE) gene with acute coronary syndrome (ACS) in patients after a coronavirus disease 2019 (COVID-19).Material and methods. The study included 100 patients (women — 50, men — 50) with ACS and prior COVID-19, verified by a polymerase chain reaction (PCR), hospitalized in the regional vascular center № 7 of the City Clinical Hospital № 2 city of Novosibirsk. The mean age of women and men was 59,5±7,2 years and 53,5±9,3 years, respectively. The diagnosis of ACS was established according to a set of criteria proposed and established by the Russian Society of Cardiology and in accordance with the updated 2020 guidelines. Patients underwent examinations, coronary angiography with stenting, as provided for in the standards of care and guidelines. In patients, the nucleotide sequence variant rs1799752 of the ACE gene was determined using PCR. The comparison group consisted of 200 patients with ACS without COVID-19 (no positive PCR or antibodies). Statistical analysis was carried out using the SPSS 17.0.5 software package.Results. When comparing the frequencies of rs1799752 genotypes of the ACE gene in groups with ACS with COVID-19 and ACS without COVID-19, significant differences were obtained (p=0,013). In the group with ACS and COVID-19, carriage of the heterozygous genotype was less common (p=0,005) and there was an accumulation of carriers of the homozygous DD genotype (1,6 times higher; 26% vs 16%; p=0,044).Conclusion. The nucleotide sequence variant rs1799752 (I/D) of the ACE gene is associated with ACS in patients after COVID-19.

Wolff-Parkinson-White syndrome (WPW) is a syndrome with early ventricular excitation due to the abnormal electrical conduction through an accessory atrioventricular pathway, and is usually accompanied by supraventricular tachycardia. There is a proven genetic component in the development of this syndrome. This review presents current literature data on the association of nucleotide sequence variants of the PRKAG2 and PRKAG3 genes in patients with WPW.

The aim of the study is to evaluate the association of some molecular genetic markers with progressive atherosclerosis. Material and methods. In total, the study included 202 patients (147 men and 55 women), who were divided into 2 groups. The 1st (main) group included patients with coronary artery disease (100 people) who had a combination of two or more cardiovascular events during the last 2 years before inclusion: myocardial infarction or unstable angina pectoris, arterial stenting for urgent indications (coronary and peripheral), stroke; acute ischemia, thrombosis or amputation of the lower extremities. The 2nd group (comparisons) included 102 patients with coronary artery disease who did not have any of the above cardiovascular events during the last 2 years before inclusion. DNA was isolated from peripheral blood samples by phenol-chloroform extraction. Results. In the group with progressive atherosclerosis at the age of 55 years and older, the AA rs3746444 genotype of the MIR499A gene was absent in both men and women, while in the control group its frequency reached 8.3 % (p = 0.044). The odds ratio of detecting the carriage of the heterozygous genotype AG of the rs6922269 polymorphism of the MTHFD1L gene in the group with progressive atherosclerosis is 0.5 times lower compared to the control group (95 % confidence interval 0.3–0.9; p = 0.034). Conclusions. Carrying the AA genotype rs3746444 of the MIR499A gene is a conditionally protective factor against the development of progressive atherosclerosis at the age of 55 years and older. Carrying the AG genotype of the rs6922269 polymorphism of the MTHFD1L gene is associated with a reduced likelihood of developing progressive atherosclerosis in patients with CAD.

Single nucleotide polymorphisms rs1008832 of the CACNA1C gene, rs4027402 of the SYNE2 gene, rs2340917 of the TMEM43 gene, rs58225473 of the CACNB2 gene were found by sequencing the clinical exome of a group of men who died of sudden cardiac death (SCD) at the age of 45 years. The aim of the study is to study the association of single nucleotide polymorphisms rs1008832 of the CACNA1C gene, rs4027402 of the SYNE2 gene, rs2340917 of the TMEM43 gene, rs58225473 of the CACNB2 gene with SCD in a case-control study using routine molecular genetic analysis. Material and methods. SCD group (n = 400, mean age 53.2 ± 8.7 years, 70.9 % men, 29.1 % women) was formed using the SCD criteria of the European Society of Cardiology from the anonymous DNA bank of the deceased sudden death (1999–2019). The control group (n = 400, mean age 53.1 ± 8.3 years, 68.3 % men, 31.7 % women) was matched by sex and age to the SCD group from DNA banks of international projects MONICA and HAPIEE of living at the time of researches participants. Genotyping was carried out using the polymerase chain reaction followed by analysis of restriction fragment length polymorphism. Results. There were no statistically significant differences in the frequencies of genotypes and alleles of single nucleotide polymorphisms rs1008832 of the CACNA1C gene, rs4027402 of the SYNE2 gene, rs2340917 of the TMEM43 gene, rs58225473 of the CACNB2 gene between the SCD group and the control group (p > 0.05). Conclusions. The association of single nucleotide rs1008832 of the CACNA1C gene, rs4027402 of the SYNE2 gene, rs2340917 of the TMEM43 gene, rs58225473 of the CACNB2 gene with SCD has not been confirmed.

The aim of the study is to evaluate the association of some molecular genetic markers with progressive atherosclerosis. Material and methods. In total, the study included 202 patients (147 men and 55 women), who were divided into 2 groups. The 1st (main) group included patients with coronary artery disease (100 people) who had a combination of two or more cardiovascular events during the last 2 years before inclusion: myocardial infarction or unstable angina pectoris, arterial stenting for urgent indications (coronary and peripheral), stroke; acute ischemia, thrombosis or amputation of the lower extremities. The 2nd group (comparisons) included 102 patients with coronary artery disease who did not have any of the above cardiovascular events during the last 2 years before inclusion. DNA was isolated from peripheral blood samples by phenol-chloroform extraction. Results. According to the frequencies of genotypes of the I/D polymorphism (rs36232792) of the SOD1 gene, no statistically significant differences were obtained between the group with progressive atherosclerosis and the control, neither in general, nor when divided by sex and age. The odds ratio of developing progressive atherosclerosis in carriers of the rare homozygous DD genotype of the rs3834129 polymorphism of the CASP8 gene is 2.3 ne is 2.3 times higher compared to carriers of the other two genotypes (DD vs II + ID, 95 % CI 1.1–5.1; p = 0.037). In men, the odds ratio is higher than in the general group – 4.4, p = 0.015. Women also tend to accumulate carriers of the DD genotype in the group with progressive atherosclerosis (26.7 % vs 16.0 %), but the differences do not reach the level of statistical significance. Conclusions. The carriage of the DD genotype of the rs3834129 polymorphism of the CASP8 gene is associated with progressive atherosclerosis in patients with CAD. No association of I/D polymorphism (rs36232792) of the SOD1 gene with progressive atherosclerosis was found. Acknowledgments. The molecular genetic fragment of the study was supported by State Budget theme no. 122031700094-5.

Subjects and methods. The study included patients with IDC (group 1; n=111, 89.2% men, average age 51.7±9.7 years) and ICM (group 2; n=110, 91.5% men, average age 58.7±8.4 years). All patients (IDC and ICM) underwent coronary angiography. Based on the anamnesis data and instrumental studies, those patients who could be said to have no risk factors for the development of dilatation of the heart cavities were identified in the group 1. And those patients who were reliably diagnosed with coronary artery disease were in the group 2, that is, dilatation of the heart cavities is due to a previous myocardial infarction, existing angina pectoris. The control group (n=121, average age 53.6±4.8 years) included patients who had no manifestations of cardiovascular diseases. The patients underwent laboratory and instrumental studies, as well as molecular and genetic studies of the A/G polymorphism of the SCN5A gene (rs1805124).Results. In the group with IDC 51.4% of patients were carriers of the common homozygous AA genotype, the heterozygous AG genotype-40.5%, and the rare homozygous GG genotype-8.1%. In the control group 63.3% of patients were identified as carriers of a homozygous genotype by a common allele, and 33.5% were carriers heterozygous genotype, and homozygous genotype for a rare allele – 3.2%. The analysis revealed a statistically significant decrease in the frequency of carrying the homozygous AA genotype in patients with IDC compared to the control group of the rs1805124 polymorphism of the SCN5A gene. In the group of patients with ICM, the А allele (69.5% vs. 80.1%, p=0.003) and the AA genotype (50.9% vs. 63.3%, p=0.030) were significantly less common than in the control group. The rare homozygous GG genotype was statically more common in patients with ICM compared to the control group (11.8% vs. 3.2%, p=0.004). Also, the G allele in the group of patients with ICM was detected statically significantly more often than in the control group (30.5% vs. 19.9%, p= 0.003).Conclusion. The polymorphic locus rs1805124 of the SCN5A gene is associated with both IDC and ICM. Homozygous genotype AA and allele A are conditionally protective factors for the development of these conditions in men.

Cerebrovascular accident (CVA) in patients with various cardiovascular diseases is a life-threatening complication, the development of which can be contributed by both environmental and genetic factors, the understanding of which is necessary to determine the tactics of treatment and predict the disease course. The article presents a brief review of studies on genetic predictors of CVA, in particular the association of the ABCA1 rs2230806 polymorphism and the risk of CVA in cardiovascular patients. Targeted studies of associations of the ABCA1 rs2230806 polymorphism with cerebrovascular diseases in the Russian Federation, except for studies at our university, could not be found.

In this literature review, we analyzed studies on the influence of genetic specifics of patients on the restoration of myocardial contractility after acute myocardial infarction. Data on the influence of genetic characteristics on the myocardial repair, remodeling process, and the restoration of cardiac contractility are presented. The use of genetic methods in the examination of patients and further consideration of individual characteristics when prescribing therapy will make it possible to implement a personalized approach to each patient. This will improve the effectiveness of treatment and the disease prognosis.

The article presents a literature review on the study of the relationship of FGA, FGB, F2, F5, PAI, ITGA2 gene polymorphisms with the development of pulmonary embolism (PE). We concluded that genetic factors in the development of PE are to a greater extent mutations in the F2, F5, PAI, ITGA2 genes. There is a positive correlation between the presence of combined genetic mutations and the development of PE. The study of allelic polymorphism of hemostasis genes makes it possible to predict coagulation system disorders, including PE.

Aim of the study was to investigate the associations of metabolic, behavioral, socio-economic risk factors and some molecular genetic markers with the risk of cardiovascular death (CVD) in persons with type 2 diabetes (T2DM) aged 45–69 years. Material and methods. The analysis included survey data from 681 participants with T2DM. The baseline survey was carried out within the framework of the HAPIEE project. The observation period lasted from 2003– 2005 to December 31, 2018 and averaged 14.7 ± 0.7 years. Persons who at the time of the baseline examination had an indication of a previous myocardial infarction and/or cerebral stroke were excluded from the analysis. The causes of CVD were determined according to the code International Classification of Diseases 10th revision – I (0–99). Within the framework of the study, 2 groups were formed: the main group, which included persons with T2DM who «developed fatal CV events» 2 207 people (107 men and 100 women) and a comparison group – persons with T2DM who «did not develop fatal CV events» for observation period – 474 people (177 men and 297 women). Indicators of anthropometry, blood pressure, socio-demographic data, some biochemical parameters and molecular genetic markers were determined. To analyze the association of the studied factors with the risk of CVD, multivariate stepwise Cox regression analysis was used. Results. The risk factors for CVD common for men and women were determined: age, increased SBP, current smoking, non-working status, fasting blood plasma glucose ≥ 7.5 mmol/L. For men, significant risk factors for CVD were also – heart rate ≥ 75 per minute, lonely status; for women – verified diabetes before the baseline examination. Carriage of the heterozygous AG genotype against the AA + GG rs2464196 HNF1A is associated with a reduced risk of fatal CV events in men, OR = 0.488 (95 % CI 0.254–0.941). Carriage of the heterozygous genotype AC rs11212617 ATM is associated with an increased risk of fatal CV events in both sexes. OR = 1.561 (95 % CI = 1.022–2.384). Conclusion. In men and women with T2DM over a 15-year follow-up, associations were found between the risk of fatal CV events with the level of both «traditional» and «diabetes-related» risk factors, as well as with the HNF1A rs2464196 and ATM rs11212617.

Purpose of the study: the aim of this work is to assess the association of 7 SNPs (rs499818 of the PHACTR1 gene, rs619203 of the ROS1 gene, rs10757278 (xr. 9), rs1376251 of the TAS2R50 gene, rs2549513 (xp. 16), rs4804611 of the ZNF627 gene and rs17465637 гена MIA3) with the severity of myocardial infarction. Materials and methods. Three samples were taken as objects of research. A population sample of patients with non-fatal MI (200 people: men – 129, women – 71), a sample of participants in the HAPIEE project with developed MI during the study (94 people: men – 56, women – 38). A sample of patients with myocardial infarction admitted to the intensive care unit of the city clinical hospital № 1. The sample size was 159 people (112 men, 47 women). The following SNPs were taken into the study: rs499818 (xp. 6), rs619203 of the ROS1 gene, rs10757278 (xr. 9), rs1376251 of the TAS2R50 gene, rs2549513 (xr. 16), rs4804611 of the ZNF627 gene and rs174653. To assess the association of SNP and the severity of the disease, we compared a population sample of patients with non-fatal MI versus a joint group from a sample of HAPIEE project participants with developed MI during the study, and a sample of MI patients admitted to the intensive care unit of City Clinical Hospital No 1. Results. For two SNPs, statistically significant differences in genotype frequencies were obtained: rs10757278 AA vs AG + GG OR = 0.61 CI 0.39–0.94; p = 0.027 and rs619203 of the ROS1 gene in a group of men for genotype GG vs CG + CCOS = 0.59 CI 0.37–0.94; p = 0.033. Conclusions. The associations of seven SNPs were studied, which, according to international studies, are associated with the risk of development, poor prognosis and the severity of myocardial infarction in the population of residents of the city of Novosibirsk. Two SNPs (rs10757278 and rs619203) were identified, which are associated with the severity of myocardial infarction.

Aim of the study was to create a method for assessing the probabilistic time of development of acute myocardial infarction (AMI) in patients with a confirmed diagnosis of type 2 diabetes mellitus (DM). Material and methods. The work was carried out on the basis of the Regional Vascular Center No. 1 (Novosibirsk). A retrospective analysis of the data of 115 patients diagnosed with AMI in combination with verified type 2 DM who were hospitalized in the period from 2018 to 2019 was performed. In all patients included in the study, clinical and demographic, anamnestic, physical, functional, and laboratory data were assessed in accordance with the federal standard for the diagnosis and treatment of this pathology. The nature and duration of the course, drug therapy for diabetes mellitus were assessed according to medical documents and databases. Further, a regression model was built for assessing the probabilistic time of development of AMI in patients with type 2 DM. Results. The author’s model for assessing the probabilistic time of development of acute myocardial infarction in patients with type 2 DM included eight indicators that significantly correlated with the dependent variable and weakly correlated with each other: patient gender, chronic kidney disease with a decrease in glomerular filtration rate to 60 ml/min/1.73 m2, diabetic retinopathy, verified peripheral polyneuropathy, cigarette smoking 1 pack or more, the number of hemodynamically significant coronary artery stenoses according to the results of selective coronary angiography, the use of short-acting insulin as part of hypoglycemic therapy, the use of long-acting insulin as part of hypoglycemic therapy. Conclusion. The study demonstrates the high predictive ability of the author’s approach for determining the individual predicted time for the development of AMI in a patient with type 2 DM. The introduction of the developed method into real clinical practice will make it possible to personally manage type 2 DM patients and to reduce the individual risk of such a formidable cardiovascular complication as myocardial infarction.

Factor V, encoded by the F5 gene, is a procoagulant blood clotting factor that increases the production of thrombin, the central enzyme that converts fibrinogen to fibrin, which leads to the formation of a blood clot. The F5 gene is localized to 1q24.2 chromosome and consists of 25 exons. There are various mutations in the F5 gene that lead to resistance of activated protein C (APC) (elimination of the APС cleavage site in factor V and factor Va), which can lead to arterial and venous thrombosis. The aim of the present study was to analyze variants of the F5 gene in patients diagnosed with coronary atherosclerosis without acute coronary syndrome with stable functional class II–IV angina pectoris, confirmed by coronary angiography data, using the method of whole exome sequencing. Material and methods. The study was conducted in the framework of the Program of joint research work IIPM — branch of the ICG SB RAS and the FSBI «Research Institute of Circulation Pathology named after E.N. Meshalkin» Ministry of Health of Russian Federation. The study included 30 men aged 40–70 years with coronary angiography-­verified coronary atherosclerosis, without ACS, with stable angina pectoris of the II–IV FC. Patients were admitted for coronary bypass surgery, and endarteriaectomy from the coronary artery (s) was performed during the operation according to intraoperative indications. Whole exome sequencing (SureSelectXT Human All Exon v.6+UTR) was carried out on an Illumina NextSeq 500 instrument (USA). Results. In 30 patients, 29 single-­nucleotide variants were found in the F5 gene. In patients with coronary atherosclerosis, rs9332701 of the F5 gene is 3.33 times more common, and rs6027 is 1.67 times more common than in the population. And rs184663825 was found in 3.33% of cases, while its occurrence in the population is 0.05%. For variants rs6034 and rs144979314, a possible damaging effect on the protein product is shown. Conclusion. The single-­nucleotide variants rs9332701, rs6027, rs184663825, rs6034, rs144979314 of the F5 gene are of interest for inclusion in the genetic panels for the analysis of risk factors for the development of acute coronary syndrome.

Introduction. The article discusses the problem of using cognitive visceral cardiobiofeedback as a preventive and non-drug method for correcting disturbed regulation mechanisms associated with an increase in blood pressure in adolescents with essential hypertension (EH) against the background of standard antihypertensive therapy with enalapril. Aim of the study was to investigate the indices of the cardiointervalogram (CIG) during a biofeedback session and to evaluate the effectiveness of cardiobiofeedback in healthy adolescents and adolescents with EH living in Novosibirsk. Material and methods. Each participant underwent a 5-minute CIG recording using the hardware and software complex VedaPulse under physiological rest and during biofeedback session. In the course of biofeedback, the subject was asked to lengthen the expiration phase of the respiratory cycle with parallel relaxation of muscle tone and visual feedback on the dynamics of a multimedia plot reflecting changes in the duration of the cardiac cycle. Results and discussion. We found that the effectiveness of cardiorespiratory synchronization (CRS) is characterized by an increase in SDNN indicators by 8.3% and the total power of spectral influences (TP) by 23.6% due to a significant increase in the parasympathetic spectral index of HF by 29.4%. An increase in the power index of the spectrum of low-frequency oscillations (LF) by 51.3% can be considered as an element of CRS within 0,1 Hz. In healthy adolescents, the reactivity of the suprasegmental levels of regulation (IC) is preserved and their growth is noted by 7.6%. In adolescents with EH, an increase in the duration of the cardiac cycle by 5.2% and TP by 31.2% was recorded in the course of cardiobiofeedback, which is associated with an increase in the power of the spectrum of high-frequency oscillations (HF) by 2.4%. This phenomenon should be considered as a positive pathophysiological response of the autonomic link of the nervous system, which is recorded by a decrease in blood pressure. Conclusion. We assume that the test with cognitive visceral cardiobiofeedback can serve as an effective marker for the analysis of the rigidity of autonomic mechanisms of regulation in adolescents with essential hypertension. Conscious regulation of the heart rate through the mechanism of controlled respiration (biofeedback) can be an effective non-drug method for correcting autonomic regulation disorders in adolescents with arterial hypertension, which is manifested by a significant decrease in blood pressure.

Aim. To study associations of rs2464196 and rs11212617 polymorphisms with the development of myocardial infarction (MI) in combination with type 2 diabetes (T2D).Material and methods. The study included two groups: main group (n=115) — patients with prior myocardial infarction and T2D, comparison group (n=116) — patients with myocardial infarction without T2D, hospitalized from December 1, 2018 to December 31, 2019 at the Regional Vascular Center № 1 of the City Clinical Hospital № 1. Participants were comparable in sex and age. Patients underwent clinical and instrumental investigations, a genetic test for single nucleotide polymorphisms, which showed associations with the development of MI and T2D according to genome-wide association study (GWAS): rs2464196 of the HNF1A gene, rs11212617 of the ATM gene.Results. Carriage of the AA genotype of the HNF1A rs2464196 polymorphism was found to be associated MI in combination with T2D in the general group (odds ratio (OR), 3,180, 95% confidence interval (CI), 1,206-8,387, p=0,015). After division of the group by sex, significant differences remained only in women (OR=9,706, 95% CI, 1,188-79,325, p=0,011).Conclusion. The data obtained can make it possible to identify a priority group of patients for personalized prevention of cardiovascular diseases.

Objective: to study the association of rs662799 with the development of acute cerebrovascular accident in patients with cardiovascular diseases and risk factors for their development. Material and methods. The material of the study was presented by 260 inpatient patients with acute cerebrovascular accident at the age of [57.0; 51.0–62.0] years as a comparison group, 272 patients aged [55.0; 51.0–62.0] years were examined, this is the control group of our study. According to gender, all patients in the main group were divided into 157 men and 103 women. There were 170 men and 102 women in the control group. All patients of the main group, along with routine methods of examination, were analyzed by the blood coagulation system, from instrumental methods of investigation-electrocardiography, echocardioscopy, ultrasound duplex scanning of extracranial brachioce phalic arteries, daily monitoring of blood pressure and heart rate, computed tomography of the brain. In patients of the main group, comorbid pathology was represented by the following cardiovascular diseases and risk factors: arterial hypertension (AG), paroxysmal supraventricular tachycardia, dyslipidemia, atherosclerosis of brachiocephalic arteries, disorders of the hemostasis system. The control group was investigated as part of the HAPIEE international project. Molecular genetic analysis was performed by real-time PCR. Statistical processing of the material was carried out using the Excel application kit and SPSS 22. The study was performed in accordance with Good Clinical Practice standards and the principles of the Helsinki Declaration. The study protocol was approved by the Ethics Committees of all participating clinical centers. Prior to inclusion in the study, written informed consent was obtained from all participants. Results. In all analyzed groups and subgroups of patients, an association was established between the rare G allele and the increased risk of PMC. The GG genotype showed significant associations with PMK in the main patient group, in the male subgroup, and in the AG subgroup. Conclusion. The AG genotype and the G allele rs662799 increase the risk of stroke in patients regardless of previous cardiovascular pathology and risk factors, including patients with arterial hypertension, supraventricular tachyarrhythmias, atherosclerosis of the brachiocephalic arteries, impaired lipid metabolism and the hemostatic system.

The aim of the research is to verify the association with sudden cardiac death (SCD) of single nucleotide polymorphisms rs7172856 and rs61999948, identified as new molecular genetic markers of SCD in the own genome-wide pooled allelotyping. Material and methods. Case-control study. The SCD group is formed using the criteria of the European Society of Cardiology from the DNA bank of suddenly deceased residents of the Oktyabrsky district of Novosibirsk (n = 437, average age – 53.1±9.0 years, men – 73.5 %, women – 26.5 %) The control group (n = 405, average age 53.2±9.2 years, men 70.0 %, women 30.0 %) is formed from the DNA bank of participants of MONICA and HAPIEE projects. DNA was isolated by phenol-chloroform extraction from myocardial tissue in the SCD group and venous blood in the control group. Genotyping was performed by the PCR-RFLP method. Results. No statistical significance was found in allele and genotype frequencies of rs7172856 between groups, even in separating in sex and age (p > 0.05). The proportion of male carriers of the TT genotype rs61999948 in the SCD group (6.3 %) is statistically significantly less than the proportion of male carriers of the TT genotype rs61999948 in the control group (12.6 %) (OR = 0.47, 95 % CI 0.26-0.85, p = 0.011). The identified significance is reserved in the group under 50 years old (p = 0.007) and in the group of men under 50 years old (p = 0.002). The proportion of carriers of the CC genotype rs61999948 is statistically significantly higher in the SCD group (59.0 %) compared with the control group (42.5 %) (OR = 1.94, 95 % CI 1.21–3.12, p = 0.006) for people under 50 years old. The identified association of the CC genotype with the SCD is reserved in the group of men under 50 years old (p = 0.001). Conclusions. Single nucleotide polymorphism rs7172856 is not associated with SCD. The TT genotype of the single nucleotide polymorphism rs61999948 is associated with a protective effect against SCD and the CC genotype of rs61999948 is associated with an increased risk of SCD for men under 50 years old.

Aim. To confirm the association between sudden cardiac death (SCD) and single nucleotide polymorphisms rs7164665, rs71461059, rs74765750, rs6762529, identified in own genome-wide associative study as new molecular genetic markers of SCD.Material and methods. As design we used case-control study. The SCD group was formed using the SCD criteria of the European Society of Cardiology (n=438, average age 53,2±9,1 years, male — 72,7%, women — 28,3%). The control group (n=435, average age 53,2±8,9 years, men — 70,0%, women — 30,0%) was selected by gender and age for the SCD group from the DNA bank of the international projects MONICA and HAPIEE. DNA was isolated by phenol-chloroform extraction from myocardial tissue in the SCD group and venous blood in the control group. Genotyping was performed by polymerase chain reaction followed by analysis of estriction fragment length polymorphism. The results are statistically processed using the SPSS 16.0 software package.Results. No carriers of the rare allele A of the single nucleotide polymorphism rs74765750 were found in the SCD group and the control group. No statistically significant differences were found between the SCD group and the control group relating to frequencies of genotypes and alleles of single nucleotide polymorphisms rs7164665 and rs71461059. In the age group older than 50 years, the proportion of carriers of the heterozygous CT genotype of the single nucleotide polymorphism rs6762529 in the SCD group is statistically significantly lower compared to the control group (CT vs CC+TT: OR=0,686, 95% CI 0,483-0,967 p=0,035).Conclusion. The CT genotype of the single nucleotide polymorphism rs6762529 is associated with a protective effect on SCD for people over 50 years of age. The association with single nucleotide polymorphisms rs7164665, rs71461059, rs74765750 with SCD has not been confirmed.

Aim. To identify genetic markers of risk for ST-elevated myocardial infarction (STEMI).Material and methods. The study included 210 patients (119 men, 91 women) with STEMI, hospitalized from December 21, 2016 to June 16, 2017 The average age of men was 55,5±9,5 years, women — 57,5±9,1 years. The diagnosis of STEMI was verified according to the criteria of the European Society of Cardiology (2015, 2017). During hospitalization, patients underwent clinical and instrumental examination, stipulated by medical care standards and clinical guidelines We also conducted a genetic study of single nucleotide polymorphisms (SNPs), which showed their association with the risk of coronary artery disease (CAD) and acute myocardial infarction (AMI) according to the GWAS: rs2820315 of the LMOD1 gene (Leiomodin 1, mapped on chromosome 1), rs9349379 of the PHACTR1 gene (regulator 1 of actin and phosphotase, localized on chromosome 6p241), rs867186 of the PROCR gene (Protein C receptor, located on chromosome 20q11.22), rsi1799883 of the FABP2 gene (Fatty acid-binding protein 2, located on chromosome 4q26). Statistical data analysis was performed using the SPSS 170.5 software package and authorial odds ratio (OR) calculator.Results. Carriage of the CC genotype of rs2820315 polymorphism of the LMOD gene is associated with an increased risk of STEMI by 1,87 times (95% CI 1,2862,722, p=0,016). Carriers of the CT genotype of rs2820315 polymorphism have a reduced risk of STEMI (OR 0,633; 95% CI 0,436-0,918, p=0,016).Conclusion. In order to identify risk groups for STEMI development, the study of the rs2820315 polymorphism of the LMOD gene is recommended. This will define the high-risk group for STEMI for developing of personalized programs for primary and secondary prevention of cardiovascular events in practical health care, which will contribute to reducing of STEMI mortality.

Aim. To determine the genetic predictors of five-year outcomes in patients with acute coronary syndrome (ACS).Material and methods. The study included patients admitted to the City clinical hospital № 1 (CCH №1) in Novosibirsk with a diagnosis of ACS in the period 2010-3 2011 (n=280). All patients were examined in accordance with clinical guidelines and standards of care, genetic markers were assessed. Genotyping included determination of single nucleotide polymorphisms (SNPs), confirming its association with the development of the ACS according to the results of an international genomeassociated studies: rs1376251, rs4804611, rs 1333049, rs619203, rs10757278, rs2549513, rs499818, rs17465637. All patients are kept in touch from the moment of initial contact to the present time, with the help of available means of communication and annual examinations in order to assess the end points. “End points” included: repeated nonfatal myocardial infarction (MI), hospitalization for myocardial ischemia, re-revascularization or chronic heart failure (CHF), nonfatal acute cerebrovascular accident (NACA), cardiovascular death.Results. We revealed SNPs, which play a role in predicting long-term outcomes of ACS: rs10757278, rs 4804611, rs 1333049, rs 2549513. The genotype of rs2549513 as 2,9-fold (95% CI 1,06-8,03; p=0,041) increases the risk of unfavorable long-term prognosis in the subgroup of men older than 55 years. The AA genotype rs10757278 and GG genotype rs1333049 are associated with a favorable long-term prognosis (OR=0,47, 95% CI 0,23-0,96; p=0,042 and OR=0,41, 95% CI 0,22-0,78; p=0,049, respectively) in the group of patients older than 55 years. For the GG genotype rs1333049 association was characteristic only for women. The AA genotype rs4804611 is associated with a favorable outcome of ACS at the age of 55 years (OR=0,036, 95% CI 0,14-0,96; p=0,053), significant differences were obtained in the group of men (p=0,36).Conclusion. The use of identified genetic predictors to assess the risk of five-year outcomes will strengthen a personalized approach to patients and, together with conventional prevention measures, will reduce cardiovascular mortality.

Aim. To study the association of single nucleotide polymorphism (SNP) rs2230806 (C>T) with the development of acute cerebrovascular accident (CVA) in East Siberian patients with cardiovascular pathology and risk factors.Material and methods. The study involved 260 patients with acute CVA (age [57,0; 51,0-62,0]) and 272 patients of control group (age [55,0; 51,0-62,0]). Among patients with acute CVA there were 157 men and 103 women. The control group included 170 men and 102 women. Examination of the experimental group included: acquisition of complaints, anamnesis, clinical examination, computed cerebral tomography, electrocardiography, echocardioscopy, ultrasound duplex scanning of extracranial brachiocephalic arteries, 24-hour monitoring of blood pressure and heart rate, analysis of the blood coagulation system. In patients of the experimental group, the following cardiovascular pathology and risk factors were present: arterial hypertension, paroxysmal supraventricular tachycardia, dyslipidemia, atherosclerosis of the brachiocephalic arteries, hemostatic system disorders. The control group was examined as part of the international HAPIEE project. Molecular genetic studies were performed by real-time PCR.Results. In all analyzed groups and subgroups of patients, a statistically significant relationship was found between the CC genotype and the C SNP allele rs662799 (A>G) and an increased risk of stroke.Conclusion. The CC genotype and the C SNP allele rs2230806 (C>T) increases the risk of acute cerebrovascular accident in patients regardless of previous cardiovascular pathology and risk factors, including in patients with arterial hypertension, supraventricular tachyarrhythmias, atherosclerosis of brachiocephalic arteries, and disorders of lipid metabolism and hemostatic system.

Aim. To study the association of single nucleotide polymorphism rs556621 (G> T) with development of stroke in patients of the East Siberian population with cardiovascular pathology and risk factors.Material and methods. The study involved 260 patients (157 men and 103 women) with stroke (mean age 57.0 [51.0-62.0]) and 272 patients (170 men and 102 women) of the control group (mean age 55.0 [51.0-62.0]). The examination of the main group included: collection of complaints, anamnesis, clinical examination, computed tomography of the brain, electrocardiography, echocardioscopy, ultrasound duplex scanning of extracranial brachiocephalic arteries, daily blood pressure and heart rate monitoring, analysis of the blood coagulation system. The patients of the main group have arterial hypertension, paroxysmal supraventricular tachycardias, dyslipidemia, atherosclerosis of the brachiocephalic arteries, disorders of the hemostatic system. The control group was studied in the framework of the HAPIEE international project. Molecular genetic research was performed by real-time polymerase chain reaction.Results. There were no statistically significant differences in the frequencies of genotypes and single nucleotide polymorphism rs556621 alleles (G>T) in the subgroup of patients with stroke and those in the control group. The frequency of the rare TT genotype among patients with stroke was 13.3%±4.16, among healthy individuals – 8.8±3.37% (p=0.1). Gender differences when comparing the frequencies of genotypes and alleles were also not detected (p>0.05). The frequencies of the TT genotype were approximately the same in the subgroup of patients with arterial hypertension (13.1%±4.22) and in the control group (7.4±5.25%; p>0.05). No significant differences were observed in the frequencies of the rare genotype of the studied polymorphism in the subgroup of patients with supraventricular tachycardias (20.0±14.37%), hypercoagulability (15.9±7.64%) and the control group (8.8±3.37%), p>0.05. A statistically significant relationship was found between the rare genotype TT of single nucleotide polymorphism rs556621 (G>T) and the development of stroke in patients with dyslipidemia and atherosclerotic lesions of the coronary arteries (p=0.041; odds ratio 1.86, 95% confidence interval 1.02-3.41).Conclusion. The genotype of TTs of single nucleotide polymorphism rs556621 (G> T) increases the risk of developing stroke in patients with dyslipidemia and atherosclerosis of the brachiocephalic arteries compared with carriers of the GG and GT genotypes. The obtained data are recommended to be considered when prescribing lipid-lowering and antithrombotic therapy.

The aim of the study was to investigate the association of SNPs in the TRPA1 (rs13268757) and TRPV1 (rs222747) genes with myocardial infarction. Material and methods. Myocardial infarction (MI) (200 individuals) and control (420 individuals) groups were formed as a part of international HAPIEE project. Genotyping the groups for the studied rs13268757 and rs222747 polymorphisms was performed by a real-time PCR on a StepOnePlus device (Applied Biosystems, USA) using TaqMan probes (Applied Biosystems, USA) according to a standard protocol. Intergroup comparison of the allele/genotype frequencies for each of the studied polymorphisms was calculated using Fisher's exact test and the SPSS 11.0 program. The correspondence of genotype frequencies to Hardy-Weinberg equilibrium was tested using the χ2 method. The relative risk of MI for a particular allele or genotype was calculated as an odds ratio (OR) using Fisher’s exact two-sided test and Pearson chi-square test. Differences were considered statistically significant with a significance level p

The aim of the work is to compare the number of copies of mtDNA in myocardial tissue in persons who died of sudden cardiac and non-cardiac death. Material and methods. Group of sudden cardiac death (SCD, 150 samples): the autopsy material was collected from those who suddenly died outside the medical and preventive treatment facilities of persons who underwent a forensic medical examination according to a standard protocol. As a control group (n = 150), a sample of individuals (selected by gender and age) was used, which, according to the conclusion of the forensic medical examination, died suddenly from other causes (SD). The study of the number of copies of mtDNA was performed in DNA samples isolated from myocardial tissue by the method of phenol-chloroform extraction, using real-time quantitative PCR (qPCR). Results. In both studied groups, there are no significant correlations of the number of copies of mtDNA with age in both men and women. In the general regression analysis, with the introduction of age into the model, the difference between the SCD and SD groups was obtained in the number of copies of mtDNA (p = 0.01). When divided by sex in the group of women, there are no differences between SCD and SD in the number of copies of mtDNA (p = 0.089). In men, differences in the number of copies of mtDNA persist between SCD and SD (p = 0.023). High variability in the number of copies of mtDNA in the myocardium was noted even within the same group in individuals of the same sex and of comparable age compared to the variability in the number of copies of mtDNA in peripheral blood leukocytes (according to the literature). This is probably due to the heterogeneity of the groups on the etiology and pathogenesis of sudden death. In men, the decrease in the number of copies of mtDNA in the group with SCD, compared with those who died suddenly from other causes, is more pronounced at the age of 50 years and older. Conclusion. The number of copies of mtDNA in myocardial tissue in men who have died of SCD is lower, compared with men who died suddenly from other causes (especially over the age of 50 years).

Aim. To study the associations of polymorphisms in F2, F7, and PAI1 genes with the presence of vulnerable plaque in coronary arteries (CA) and the blood concentration of proteins encoded by these genes.Material and methods. The study included 101 men 40-70 years old with documented coronary atherosclerosis, who underwent coronary artery bypass grafting. According to the histological analysis of atherosclerotic plaques, men were divided into 2 groups: 40 men (39,6%) with stable plaque; 61 men (60,4%) with vulnerable plaques in CA. Genotyping of rs1799963 and rs6046 was performed by reverse transcription polymerase chain reaction, rs1799889 — by polymerase chain reaction. Statistical processing was performed using the SPSS 16.0 software package.Results. In patients with stable plaques, allele A of rs6046 polymorphism in the F7 gene was observed in 2,9 times more often (95% confidence interval (CI), 1,20-7,20, p=0,021) than in men with vulnerable plaques. The odds ratio of the GA genotype carriage is 4,03 times higher among patients with stable plaques in CA compared with vulnerable plaques (95% CI, 1,49-10,93, p=0,006). The odds ratio of the 5G/4G genotype carriage among patients with stable plaques in CA is 2,47 times higher than in patients with vulnerable plaques (95% CI, 1,08-5,62, p=0,039). The 4G/4G genotype carriage is 5,85 times much more common in men with stable plaques (95% CI, 1,61-21,34, p=0,003).Conclusion. Polymorphism in the PAI1 (rs1799889) and F7 (rs6046) genes are associated with the presence of vulnerable plaques in CA in men with verified coronary atherosclerosis. There were no differences between the groups in the frequencies of genotypes and alleles of the rs1799963 polymorphism of the F2 gene. Also, no significant differences were found in the blood levels of PAI-1 and factor VII in groups with different genotypes.

Aim. To search for causal mutations in candidate genes responsible for the development of sudden cardiac death (SCD) in men who died under the age of 45.Material and methods. The SCD group (n=37) was formed using the criteria the World Health Organization and the European Society of Cardiology. Autopsy material was collected from men who died suddenly outside medical institutions and underwent forensic medical examination according to the standard protocol. Autopsy revealed no morphological changes that could explain sudden death. The mean age was 32,4±6,4 years. Genomic DNA was isolated from myocardial tissue using phenol-chloroform extraction. Clinical exome sequencing was performed. At first, we analyzed the results of sequencing of 24 genes, mutations in which lead to cardiovascular diseases associated with an increased risk of SCD: KCNQ1, KCNH2, SCN5A, AKAP9, ANK2, CACNA1C, CALM1, CALM2, CAV3, KCNE1, KNCJNE2, KCNE2, SCN4B, SNTA1, MYH2, APOB, KCNA5, TGFB3, NEB, PDX1, FLNC, PLEC, KCND3.Results. Of 37 samples, we revealed 13 probable pathogenic missense mutations in 9 samples (24,3%). Of 13 probable pathogenic variants, 5 were new.Conclusion. This pilot study provides following conclusions: it is necessary to continue molecular autopsy research in Russia; to increase the effectiveness of detecting causal mutations, it is necessary to reduce the age of patients with SCD included in the study; studying the families of deceased; cooperation of experienced specialists — forensic pathologist, laboratory geneticist, cardiologist.

Aim. To study the relationship of matrix metalloproteinase-3 (MMP3) genetic polymorphism and dilated ischemic cardiomyopathy (DCM), as well as idiopathic cardiomyopathy (ICM) of unknown etiology.Material and methods. A total of 221 patients with DCM and ICM were examined (mean age, 55,30±9,69 years). The group of ischemic DCM consisted of 111 people (99 men (89,2%) and 12 women (10,8%)). The mean age of DCM subjects was 51,73±9,74 years (male subgroup, 51,00±8,96 years; female subgroup, 57,75±3,71 years). The ICM group consisted of 110 people (100 men (91,5%) and 10 women (8.5%)). The mean age of ICM subjects was 58,68±8.38 years (male subgroup, 58,29±8.,6 years; female subgroup, 62,90±6,29 years). The control group of subjects (n=121) consisted of healthy people without cardiovascular diseases (mean age, 53,6±4,8 years). All patients of the experimental group underwent routine diagnostic tests, as well as coronary angiography. In case of suspected myocarditis, cardiac magnetic resonance imaging was performed. All patients underwent polymerase chain reaction to determine the MMP3-11715A/6A polymorphism (rs35068180).Results. In patients with cardiomyopathy, regardless of the disease origin, significant differences were verified in comparison with the control group. Allele 6A (65,8% vs 59,3%, p=0,044) and genotype 6A/6A (42,1% vs 32,6%, p=0,099) were found significantly more frequently in patients with cardiomyopathy than in the control group. In addition, despite various etiological factors, the pathogenetic involvement of MMP3 is likely to have a general direction.Conclusion. In all patients with cardiomyopathy, the prevalence of MMP3 gene A allele was shown. Due to decrease in the transcription activity in homozygous 6A allele, the stromelysin level in arterial walls also decreases. This promotes the activation of procollagenase-1, the deposition of extracellular matrix and cardiac remodeling

Aim: to form a panel of genetic markers for analyzing the risk of long-term adverse prognosis of cardiovascular diseases in Russia population. Material and methods. A sample of nine hundred individuals was formed within the framework of the HAPIEE project (age 45-69 years, middle age 53.9 ± 6.9, male/female - 50/50). Molecular genetic analysis was performed using PCR followed by restriction fragment length polymorphism analysis for the APOC3 gene rs5128 polymorphism, APOE gene rs429358 and rs7412, CETP gene rs708272, LPL gene rs320, SCARB1 gene rs5888, and SREBF2 gene rs2228314 . Results. 10 single nucleotide polymorphisms were analyzed for the inclusion in the risk model of adverse prognosis of cardiovascular diseases in Russia population. The APOE gene e4/e4 genotype (rs429358 and rs7412) was associated with the development of adverse cardiovascular outcomes for 7 years of observation. For the CETP gene rs708272, the association with the development of cases of fatal myocardial infarction for 7 years of observation was demonstrated for the genotypes carrying C allele. No statistically significant association with the risk of adverse prognosis of cardiovascular diseases was obtained for the APOC3 gene rs5128, LPL gene rs320, SCARB1 gene rs5888, and SREBF2 gene rs2228314 in this pilot study. Conclusions. Pilot data on the presence of statistically significant association with the risk of long-term adverse prognosis of cardiovascular diseases in Russia population were obtained for the APOE and CETP genes.

Aim. To identify the factors of long-term adverse prognosis of patients with acute coronary syndrome as a result of five-year follow-up.Material and methods. The study included 280 patients with ACS hospitalized in the 1st cardiology Department of the Novosibirsk municipal CLINICAL hospital № 1 in 2010-2011. The study cohort included 145 patients with ACS (107 men and 38 women), 135 patients with ACS (93 men and 43 women). The average age of men was 56,3±5,2, women 52,1±5,3 years. The criteria of the European society of cardiology (2015, 2017) were used for the diagnosis of ACS. For five years, all patients included in the study were contacted through communication and annual medical examinations, to which patients were invited to the clinic. The examinations included the following clinical and instrumental examinations: clinical examination, electrocardiography, Holter monitoring of electrocardiogram, echocardiography, lipid profile, inflammatory cytokines and molecular genetic parameters. In the study, a mathematical model for predicting five-year outcomes Oxpt and Oxbt. Results. Five-year observation allowed using the constructed mathematical model to determine not only the place of each factor in the cardiovascular prognosis, but also to assess how the role of these prognostic markers changes over time. Conclusion. The use of a mathematical model for predicting long-term adverse outcomes of ACS allows to assess the value of specific risk factors and predictors, respectively, makes a significant contribution to the optimization of secondary prevention and personalized approach to treatment. At the same time, the influence of the identified predictors weakens in proportion to the increase in the number of years from a vascular accident. Thus, the identified risk factors have the maximum impact in the first year after ACS, in subsequent years, the role of these factors is reduced, which is probably due not only to the importance of the factors themselves, but also to the addition of other risk factors to the overall picture of the disease of patients. Nevertheless, the use of this model is necessary to solve the problem of reducing cardiovascular risk.

Genetic background of hypertension (AT) and blood pressure (BP) regulation is extensively investigated in genome-wide association studies (GWAS). The findings from recent GWAS require replication in independent samples.Aim. To investigate the association between BP and AT in Russian population and several single nucleotide polymorphisms identified in GWAS.Material and methods. In the frame of “case-control” design we recruited subjects with AT diagnosed at age below 50 according to the criteria of BP >140/90 mm Hg and/or receiving antihypertensive therapy, and subjects with normotension according to 2 examinations from population sampling, Novosibirsk, totally included 514, men/women aged 45-69 years). From published GWAS we selected 24 genetic markers related to hypertension, 8 markers were included for present analysis (rs 13082711, rs1173771, rs13107325, rs3918226, rs1799945, rs805303, rs1458038, rs932764). Standard epidemiological methods were used (BP measurement, anthropometry, medical history of AT and treatment, risk factors of AT, socio-demographic parameters). Single nucleotide polymorphisms (SNPs) were tested using real time PCR.Results. In studied sample we replicated the association between rs3918226 (promoter region of gene of endothelial NO synthase; eNOS) and systolic BP (T-allele carriers had 9 mm Hg higher systolic BP than CC carriers in men, p=0,049 independent of age). New association was found between rs 932764 (gene of phospholipase-c-epsilon-1 isoform, PLCE1) and AT (heterozygotes genotype AG was protective in men, p=0,017 independent of age and body mass). The association between rs13107325 (gene of soluble carrier family 39/zinc transporter/member 8, SLC39A8) and systolic BP was confirmed (in men, С-allele carriers had higher systolic BP values then TT carriers, p=0,044, multivariable adjusted).Conclusion. In analysis of relationship between phenotypes of BP and AT and 8 genetic markers of AT in Russian population sample we replicated two known associations, revealed new association and identified new data on modulating effect of sex and body mass. These replications in newly studied Siberian population, different from early studied populations by risk factors profile, climate, geographic and other parameters, support the involvement of identified or close loci in potential mechanisms of AT susceptibility.

Aim. To confirm association between sudden cardiac death (SCD) and single nucleotide polymorphisms rs6582147 rs 10010305, rs2136810, rs17797829, identified as the most likely candidate markers.Material and methods. The SCD group (n=360, mean age 53,0±9,2 years, men — 76,9%, women — 23,1%) was formed using the SCD criteria of the European Society of Cardiology. The control group (n=402, mean age 52,9±9,1 years, men — 69,7%, women — 30,3%) was selected by gender and age from the DNA bank of international studies MONICA, HAPIEE. DNA is separated by phenol-chloroform extraction. Genotyping was performed by polymerase chain reaction followed by analysis of restriction fragment length polymorphism.Results. The GT rs6582147 genotype is associated with a protective effect on SCD (OR=0,671, 95% CI 0,496-0,909, p=0,011), and the GG genotype with an increased risk of SCD (OR=1,598, 95% CI 1,195-2,135, p=0,002). The greatest effect was in the group of men over 50 years old (p

Aim. To study the association of new polymorphisms with sudden cardiac death (SCD) in men.Material and methods. The SCD group (n=278) was formed using guidelines of the World Health Organization and the European Society of Cardiology. The autopsy material was taken from the men who died suddenly outside the prevention and treatment facilities who underwent medicolegal examination according to a standard protocol. The average age in the SCD group was 53,2±8,7 years. The control group (n=274) was selected by sex and age from the DNA bank formed during the international studies of MONICA and HAPIEE. The mean age of men in the control group was 53.±8,3 years. Genomic DNA was separated from myocardial tissue and venous blood by the method of phenol-chloroform extraction. Rs10503929, rs7121, rs6730157, rs11720524, rs7737692, rs7521023 polymorphisms were tested using real-time PCR. The insertion- deletion polymorphisms rs.0692285 and rs39.7 were genotyped by PCR with flanking primers followed by polyacrylamide gel electrophoresis. Statistical analysis was performed using the SPSS 13.0 software package.Results. By comparison the frequencies of rs7121 genotypes in the studied groups of Novosibirsk, an increase in the proportion of CC genotype carriers in the group with SCD (OR=.6, 95% CI 1,1-2,2; p=0,025) was found. The carriage of the rs.0692285 ID genotype reduces the risk of SCD (OR=0,6, 95% CI 0,4-0,9; p=0,0M). A carriage of the rs39.7 ID genotype increases the risk of SCD (OR=.5, 95% CI 1,1-2,2; p=0,020).Conclusion. The rs7121 of the GNAS gene, the rs.0692285 of the RYR2 gene, and the rs39.7 of the COL1A2 gene are associated with SCD. Rs10503929, rs6730157, rs11720524, rs7737692, rs7521023 polymorphisms do not associate with SCD in the men of Novosibirsk.

Aim. To study association between polymorphisms of candidate genes and the development of non-infectious and infectious endocarditis (IE).Material and methods. During the study 175 patients were examined. They were divided into two groups: the first group — 81 patients with non-infectious endocarditis and the second one — 94 patients with IE. We present a comparative analysis of the genotype frequencies of the five genes polymorphisms: rs11697325 (-8202 A/G) of the MMP9 gene, 4a/4b of the NOS3 gene, rs4340 of the ACE gene, rs2476601 (С1858Т) of the PTPN22 gene, rs231775 (49 A/G) of the CTLA4 gene in groups of patients with endocarditis and healthy individuals.Results. We found association between endocarditis and rs11697325 (-8202 A/G) of the MMP9 gene, 4a/4b of the NOS3 gene, as well as rs2476601 (C1858T) of the PTPN22 gene with IE.Conclusion. Thus, association between three of the five polymorphisms and vegetations on the valvular heart apparatus was revealed.

Aim. To establish associations of polymorphisms of candidate genes coding for the components of the endothelial (NOS3, MTHFR) and sympathoadrenal systems (ADRB1, ADRA2B) with coronary heart disease (CHD) in the cohort of the small population of Mountain Shoriya.Material and methods. A clinical and epidemiological study was conducted in the areas of Mountain Shoriya (Orton, Ust-Kabyrza, Sheregesh, Tashtagol). Analysis of risk factors included recording the age, sex, body mass index, waist circumference, presence/absence of arterial hypertension (AH), smoking, and the presence of disorders of lipid and carbohydrate metabolism. CHD diagnosis was made by three epidemiological criteria: coding of the electrocardiogram according to the Minnesota code, Rose questionnaire, and a history of myocardial infarction. The patient underwent molecular genetic testing. DNA isolation from blood was carried out by the method of phenol-chloroform extraction. Statistical processing was carried out using the programs STATISTICA 6.1 (StatSoft Inc., USA) and SNPStats. Results. The prevalence of CHD in the Shoriya cohort was 9,7%. The results of our study established the relationship of genetic markers of the sympathoadrenal and endothelial systems with coronary atherosclerosis in the indigenous population of Shoriya. The high risk of atherosclerotic heart disease was associated with the 4b/4a genotype of the NOS3 gene (OR 2,57 95% CI (1,12-5,86), p=0,026) according to the dominant mode of inheritance. The relationship of the T/T genotype of the MTHFR gene with CHD by recessive inheritance was established (OR 13,28; 95% CI (1,79-98,40), p=0,024).Conclusion. Due to genetic research, there is a real opportunity not only to carry out accurate molecular diagnostics, but also to determine an underlying risk for a disease. Detection of genetic disposition to CHD can be carried out long before the onset of clinical symptoms, which can effectively prevent its development.

Aim. To study the combined effect of cardiovascular risk factors and genetic markers that encode the proteins of the main components of neurophysiological systems (renin-angiotensin-aldosterone, sympathetic-adrenal systems, endothelial dysfunction) on the development of arterial hypertension among the indigenous and non-indigenous population of Mountain Shoriya.Material and methods. We performed a clinical and epidemiological study of the compactly settled population in the remote areas of Mountain Shoriya. This region of middle mountains is situated in the south of Western Siberia. We examined 1409 subjects (901 subjects – the representatives of indigenous nationality [the Shors], 508 subjects – representatives of non-indigenous nationality [90% among them were the representatives of the European ethnicity]). Hypertension was diagnosed according to the National Guidelines of the Russian Society of Cardiology/the Russian Medical Society on Arterial Hypertension (2010). All patients underwent clinical, laboratory and instrumental investigation. Polymorphisms of genes ACE (I/D, rs 4340), АGT (c.803T>C, rs699), AGTR1 (А1166С, rs5186), ADRB1 (с.145A>G, Ser49Gly, rs1801252), ADRA2B (I/D, rs 28365031), MTHFR (c.677С>Т, Ala222Val, rs1801133) and NOS3 (VNTR, 4b/4a) were tested using polymerase chain reaction.Results. Cardiovascular risk factors associated with hypertension in cohort of Shorians: hypercholesterolemia [Odds Ratio (OR) 1.54, low density lipoproteinemia (OR 1.48), violation of carbohydrate metabolism (OR 1.53), obesity (OR 2.25), including its abdominal type (OR 1.53), the family anamnesis of early cardiovascular diseases (OR 1.88)] and rs4340 polymorphisms of the ACE gene (OR 4.39), rs5186 of the AGTR1 gene (OR 10.02); in the cohort of the non-indigenous ethnos – hypercholesterolemia (OR 1.87), hypertriglyceridemia (OR 1.87), obesity (OR 2.75), abdominal obesity (OR 2.73), family anamnesis of early cardiovascular diseases (OR 2.48), the polymorphism rs5186 of the AGTR1 gene (OR 26.77). Genotype G/G ADRB1 gene was characterized by protective effect against hypertension in the Shorians.Conclusion. Evaluation of the complex influence of clinical and genetic factors on the development of hypertension in the population of Mountain Shoriya showed their comparable importance among the indigenous population and the predominance of non-genetic factors among the non-indigenous population.

The review provides information on studies that have studied the relationship between the number of copies of mitochondrial DNA (mtDNA) in peripheral blood leukocytes with coronary heart disease and sudden cardiac death (SCD). Mitochondrial dysfunction is a major component of the aging process and can play a key role in the development of cardiovascular diseases of atherosclerotic origin, and the number of copies of mtDNA is an indirect biomarker of mitochondrial function. According to a number of studies, measuring the number of copies of mtDNA in peripheral blood leukocytes can improve the risk assessment of CVD to decide on the beginning of primary prevention of CVD. So far, relatively few such studies have been carried out. Nevertheless, the results obtained, according to the authors, allow us to hope that this indicator can be used in assessing the risk of individual CVD. Further studies carried out on large groups in a prospective design should provide the necessary additional information on the feasibility of including this indicator in the appropriate risk meters.

The dangerous electrophysiological shifts in the myocardium, with the exception of rare congenital canalopathies, are overwhelmingly secondary, being a consequence of various pathological conditions. These processes, in turn, can also be genetically determined. Thus, the association of indices of ventricular repolarization with polymorphism of adrenoreceptor genes is shown. The electrical instability of the myocardium, apparently, has a multigenic and multifactorial basis. The aim of the study was to study the relationship between the risk factors and the polymorphism of the ADRB1 gene with pro-arrhythmic electrocardiographic patterns in the general population of Novosibirsk. Material and methods. Materials of epidemiological study of the general population of Novosibirsk under the WHO project «MONICA» (a sample of 831 men aged 25-64 years) were used. For genetic research 195 people were randomly selected. ECG-patterns were identified in a 30 % subsample - 261 people. The number of people with both genetic and electrocardiographic data was 105 people. According to the WHO criteria, components of the metabolic syndrome were identified. The A145G (rs1801252) polymorphism of the ADRB1 gene was determined. The Brugada, early repolarization, QRS fragmentation patterns were detected according to current criteria. The multivariate general linear model (GLM) were applied. Results. The QRS fragmentation was independently associated with obesity ( p = 0.014), increased TG level ( p = 0.040), decreased HDL cholesterol level ( p = 0.00079) and polymorphism of the ADRB1 gene (p = 0.00019). Conclusion. The integral approach is advisable in analyzing the genetic, metabolic and electrophysiological factors causing the electrical instability of the myocardium.

Background. The search for genetic predictors of stroke development is actively studied in all developed countries due to the need to address the primary prevention of socially significant diseases. Gene CYP17A1 is one of the many genes that can participate in the formation of predisposition to the development of stroke.Aim. To examine association of the single nucleotide polymorphisms rs1004467 CYP17A1 gene with the development of stroke.Material and methods. The study included 184 patients with stroke (active group; 113 men and 71 women; mean age 55.06±9.40 years), 131 of them with ischemic stroke and 41 with hemorrhagic stroke. The comparison group included 251 people with hypertension without stroke (160 men and 91 women; mean age 59.21±6.62 years) and control group – 157 persons without cardiovascular diseases (106 men and 51 women; mean age 54.94±6.64 years). Study participants underwent clinical (collection of complaints, anamnesis, physical examination), laboratory (blood chemistry, lipid profile) and instrumental (computer tomography of the brain, ultrasound duplex scanning of extraand intracranial blood vessels, electrocardiography, echocardioscopy) examination to verify the diagnosis, molecular genetic study of gene polymorphism СУР17А.Results. The study established the association of homozygous genotype AA rs1004467 CYP17A1 gene with the risk of stroke, which is confirmed bya statistically significant increase in the number of carriers of homozygous genotype AA in the common allele A rs1004467 CYP17A1 gene in patients of the main group (73.4±3.3%) compared to the control group (61.8±3.9%; p=0.03). Statistically significant increase in the number of carriers of genotype AA rs1004467 of CYP17A1 gene in patients with hemorrhagic stroke (70.7±7.1%) compared with the control (61.8±3.9%; p=0.01) was revealed. There are no statistically significant associations between the rs1004467 genotypes of CYP17A1 gene and the risk factors of stroke (hypercholesterinemia, burdened hereditary, hypertension, increased intima-media thickness of brachiocephalic arteries).Conclusions. The ability to consider the genetic determinants of brain stroke allows to identify proactively the risk factors of this complex cascade process. Studies of gene polymorphism as a factor of genetic predisposition to various human diseases allow to determine the individual possibilities of optimal therapy for each patient, considering the identified risk factors.

Background. The study of the incidence of risk factors (RF) of stroke for primary and secondary prevention of this disease remains relevant. There are modifiable and non-modifiable RF.Aim. To study the frequency of the main RF in patients with ischemic and hemorrhagic stroke in the urban population of Krasnoyarsk (Eastern Siberia).Material and methods. Examination of 124 patients with an ischemic stroke and 28 with hemorrhagic was performed. Patients received treatment in neurologic center of Krasnoyarsk in 2014 year. The main criterion of inclusion was the confirmed diagnosis of an ischemic or hemorrhagic stroke. All patient had the clinic-tool and neurovisualizing examination and collecting the individual and family anamnesis with examination of modifiable and non-modifiable RF. The research of the neurologic status at patients both with ischemic, and with a hemorrhagic stroke was conducted by the standard technique. Based on results of computer or magnetic resonance imaging of a brain the diagnosis of an ischemic or hemorrhagic stroke was established.Results. A distinctive feature of patients with hemorrhagic stroke was the occurrence of a vascular accident in younger age (6 years earlier) in comparison with ischemic stroke. Among patients with ischemic stroke elevated body mass index (BMI) was in 87 (70.2%) patients, burdened heredity was in 8.1% of cases, and 43.5% of patients were smokers. Among patients with hemorrhagic stroke 16 (57.1%) patients had elevated BMI. People with burdened heredity were not identified among them. Smoking was found in 22 (78.6%) patients in this group.Conclusion. Improvement of treatment and prevention of an ischemic stroke are in many respects connected with clarification of RF and pathogenic mechanisms of its development. The rational pharmacotherapy directed to pointed impact on individual RF can reduce the risk of development of stroke not only at individual, but also at the population level.

Aim. Evaluation of the association of rs17465637 gene MIA3 (1q41), rs4804611 gene ZNF627 (19p13.2), rs2549513 (16q23.1), rs619203 gene ROS1 (6q22), rs1333049 (9p21.3), rs1376251 gene TAS2R50 (12p13.2) with arterial hypertension (AH), myocardial infarction (MI), metabolic syndrome (Ms) and coronary atherosclerosis (CAS) in Yakutia inhabitants depending on ethnicity and gender.Material and methods. The results analyzed, of the assessment of the patients with verified CAS (396 males, 60 females) and persons with no clinical signs of CHD (212 males, 271 females) age 45-64 y.o., from native and non-native Yakutia ethnicities. The period of the study: 2007-2010 years. Genomic DNA was extracted from venous blood by phenol-chlorophorm method. Genes polymorphism was tested with PCR real time according to the manual of the equipment (probes TaqMan , Applied Biosystems, USA) on the device ABI 7900HT. In the study, the following mononucleotide polymorphisms were included (MNP): rs17465637 gene MIA3, rs4804611 gene ZNF627, rs2549513 (chr. 16), rs619203 gene ROS1, rs1333049 (chr. 9), rs1376251 gene TAS2R50. For diagnosis of Ms, IDF 2005 criteria were applied.Results. Association of AH was found in native inhabitants — males with genotype СС rs1376251 gene TAS2R50 (p=0,004), in females with АА rs2549513 (chr. 16) (p=0,028) and rs4804611 gene ZNF627 (p=0,033); in non-native inhabitants (regardless the gender and in females) — rs619203 gene ROS1 (p=0,000). Relation was found for MI in native inhabitants with genotype ТТ rs1376251 gene TAS2R50 (p=0,005); in non-native heterozygous males rs17465637 gene MIA3 (p=0,047) and rs619203 gene ROS1 (p=0,009), as homozygous АА rs2549513 (chr. 16) (p=0,041). The associations were found for Ms among native inhabitants in male carriers of genotypes АА rs17465637 gene MIA3 (p=0,029) and heterozygous rs4804611 gene ZNF627 (p=0,034), as heterozygous regardless the gender rs2549513 (chr. 16) (p=0,016) in non-native inhabitants in male (p=0,016) and female (p=0,005) carriers of GG rs619203 gene ROS1 and heterozygous females rs1333049 (chr. 9) (p=0,031). With the CAS, the association found in native heterozygous males rs17465637 gene MIA3 (p=0,040) and carriers of ТТ rs1376251 gene TAS2R50 (p=0,006); in non-native males with CG rs619203 gene ROS1 (p=0,020), in nonnative females with АА rs4804611 gene ZNF627 (p=0,008), heterozygous rs1333049 (chr. 9) (p=0,030) and rs2549513 (chr. 16) (p=0,024).Conclusion. First time in inhabitants of Yakutia REpublic, the genome wide results replicated, of the association study with AH, MI, Ms, CAS. These genetic markers can be utilized for the risk assessment of cardiovascular diseases in Russian (Yakutia) population.

Aim. To evaluate the utilization of complex significance evaluation in Russian population, of genetic markers of myocardial infarction identified in entire-genomic associative studies.Material and methods. Group of MI patients (n=200) and control group (n=420) were created based on populational selection of 45-69 year old citizens of Novosibirsk (9400 persons), collected during the international project HAPIEE; myocardial infarction patients, admitted to intensive care unit of the Hospital № 1 (160 persons); sudden cardiac death victims, post forensic investigation (n=285). Longevity group was collected during home visits and in the nursing houses (n=85). Genomic DNA was extracted from venous blood and myocardial tissue by phenolchlorophorm method. Genes polymorphism was tested with PCR real-time according to the protocol by equipment developer (TaqMan, Applied Biosystems, USA), device ABI 7900HT. For the study, the following MNP were selected: rs499818, rs619203, rs10757278 and rs1333049 (chr. 9), rs1376251, rs2549513, rs4804611, rs17465637.Results. Mononucleotide polymorphisms, that did not show differences at pretest stage, showed significant distinctions in the studied population. Two MNP were closely linked: rs10757278 and rs1333049 (chr. 9) so for further assessment the rs1333049 was retained. Among other seven, only five MNP showed relation with MI of various strength. Some, like the rs1333049 showed association with MI in all groups and subgroups, while the others — only in separate groups, with restriction by sex and gender. The rs2549513 and rs17465637 showed to be not associated with CHD at all, though rs2549513 showed association with lipid and glucose metabolism, as with the severity of coronary atherosclerosis and adverse prognosis for 1 year post-MI. The rs17465637 was just poorly associated with BMI.Conclusion. Complex approach to assessment of polymorphism role is quite demanding, but provides with a high grade of insurance in the significance of the results obtained, of non-random character of the results, and makes it to choose the most credible, that have showed association not only with the main pathological phenotype, but with its risk factors.

Aim. To check the association of sudden cardiac death (SCD) with mononucleotide polymorphisms rs62116755 gene GACAT3, rs12170546 gene PARVB, rs16994849 gene PLCB1, rs78143315 gene PDCD6IP, that were set as genetic markers of SCD in previous full-genome associative original study.Material and methods. Group of SCD (n=388, mean age 52,9±9,2 y.o., males — 77,2%, females — 22,8%) was formed by the SCD criteria of World Health Organization and European Society of Cardiology. Controls matched by sex and age (n=387, mean age 52,4±8,8 y.o., males — 62,3%, females — 37,7%) from the DNA banks of international studies MONICA, HAPIEE. Separation of DNA was done with the phenol-chlorophorm extraction. Genotyping was done by polymerase chain reaction with further polymorphism analysis of the lengths of restrictional fragments.Results. There was no association with SCD of the mononucleotide polymorphisms rs62116755 gene GACAT3, rs78143315 gene PDCD6IP. In SCD group the number of TT carriers rs12170546 gene PARVB was significantly lower than in controls (OR =1,66, 95% CI 1,25-2,21, p=0,001; OR =0,67, 95% CI 0,50-0,90, p=0,009, respectively). In the group younger than 50 y.o. the number of GG carriers rs16994849 gene PLCB1 was significantly higher, and of genotype AA — lower, comparing to the controls (OR =4,92, 95% CI 1,01-23,20, p=0,032; OR =0,54, 95% CI 0,31-0,93, p=0,029, respectively). In males older than 50 the part of GG carriers rs16994849 gene PLCB1 was significantly lower than in control group (OR =0,11, 95% CI 0,01-0,91, p=0,024).Conclusion. Mononucleotide polymorphisms rs62116755 gene GACAT3, rs78143315 gene PDCD6IP were not related to SCD. Genotype ТТ of polymorphism rs12170546 gene PARVB is a genotype of risk of SCD, and genotype TC is protective. Genotype GG of polymorphism rs16994849 gene PLCB1 is the genotype of risk for SCD for those younger than 50 y.o. and is protective in those older than 50. Genotype AA of polymorphism rs16994849 gene PLCB1 is protective against SCD in those younger 50 y.o.

Aim: Investigate relations of 8 SNPs with myocardial infarction in groups of up to 55 years and after 55 years. Methods: The group of patients with myocardial infarction, arrived in the intensive care unit City Clinical Hospital № 1 (2009-2010 gg.) 160 people (113 men and 47 women). The control group was formed based on the sample of population 45-69 year old residents of the October and the Kirov district of Novosibirsk (9.400 people), which was collected by Institute of Internal Medicine SB RAMS during the work on the international project HAPIEE (Health, Alcohol and Psychosocial factors In Eastern Europe). It included 420 people with no signs of myocardial infarction (men 270, women 150). Genomic DNA was isolated from venous blood by phenol-chloroform extraction. SNP of gene were tested by RT-PCR according to the protocol of the manufacturer (TaqMan Probes, Applied Biosystems, USA) on the device ABI 7900HT. In a study following SNPs were taken: rs499818, rs619203, rs1333049, rs1376251, rs2549513, rs4804611, rs17465637. Results: For rs1333049 were shown an association with MI: SS OR = 2.05 (95 % CI 1.35-3.12 p = 0.001, CC vs CT + TT) and PT OR = 0.59 (95 % CI 0.37-0.93; p = 0.023; CT vs CC + TT) in the group. In both age groups, an association has been confirmed: SS OR = 2.92 (95 % CI 1.39-6.16; p = 0.006; CC vs CT + TT) for junior and SS OR = 1.77 (95 % CI 1.05-2.97; p = 0.035; CC vs CT + TT) and senior groups. For rs4804611 shows a predisposing role in relation to MI AA OR = 1.63 (95 % CI, 1.03-2.45; P = 0.04; AA vs AG + GG) in the older age group, for the remaining SNPs statistically valid data has been received. Conclusions: Thus in this study were confirmed by rs1333049 association (hr. 9) with myocardial infarction, regardless of age, as well as shows the association of rs4804611 in the group over 55 years.

The review systematized modern concepts of markers of endothelial dysfunction and disorders of hemostasis (asymmetric dimethylarginine, endothelin 1, adhesive ICAM and VCAM molecules, apolipoproteins, antithrombin III, receptor of urokinase plasminogen activator, tissue factor pathway inhibitor, blood coagulation factors VII, XII, prothrombin) associated with atherogenesis, and genes responsible for their regulation.

Atrial fibrillation (AF) is one of the most prevalent tachiarrhythmias, with at date non fully understood etiology. Recently, the attention is paid to genetic determinants of AF.Aim. To assess the role of rs2200733 polymorhpism on the chromosome 4q25 in development of AF in Russian population.Material and methods. Totally, 76 patients studied with AF, and control group, number 73 persons without cardiovascular pathology. All participants underwent laboratory and genetic investigations.Results. A statistically significant prevalence of genotype ТТ is found (21,21% vs 4,11%, р=0,015) and allele Т (34,85% vs 19,86%, р=0,03) in the group of patients with the lone AF comparing to the controls. Therefore, TT genotype and T allele of rs2200733 chromosome 4q25 could be predictors of unknown origin AF development.

Aim. To study the association of polymorphisms rs1800795 of gene IL-6 with the development of sick sinus node syndrome (SSS).Material and methods. Totally, 109 patients studied, with idiopathic SSS, and 59 of their healthy relatives of I, II, III grade of relation, and 173 controls. Patients from main group were selected to subgroups according to sex and clinical type of the disease. All patients underwent standard clinical and instrumental cardiological assessment and molecular-genetic test of DNA. Statistics was done with software “Statistica 7.0”.Results. There was significant predominance of homozygous genotype of rare allele of the studied gene in controls (18,5%±3,0) comparing to idiopathic SSS patients (8,5%±3,1), p=0,039, and to subgroup of males with SSS (5,2%±8 among SSS males versus 30,8%±9,1 among controls, р=0,03). Also there was significant predominance of the widespread genotype IL-6 among males with compensated SSS variant (69,2%±12,8) comparing to the controls (23,1%±8,3, р=0,005).Conclusion. Probably the homozygous genotype GG of gene IL-6 is protective against idiopathic SSS.

Aim. To study the association of the hereditary sick sinus syndrome (SSS) with gene α2B-adrenergic receptor (ADRA2B) polymorphism.Material and methods. 29 families with hereditary primary SSS from the database of the Chair of Therapy № 1 of Krasnoyarsk State Medical University named after prof. V.F. Voyno-Yasenetsky were included in the study. Group 1 included probands (20 women and 9 men, 58±0.15 y.o.), group 2 – proband relatives of I, II and III degree (65 males and 68 females, 39±0.13 y.o.), group 3 (control) — 89 healthy volunteers. Clinical examination (physical examination, ECG, bicycle ergometry, ECG monitoring, atropine test, electrophysiological study, echocardiography) was performed in all probands and their relatives. The diagnosis of SSS was confirmed by transesophageal left atrium stimulation in 75 individuals. Genotypic examination of gene ADRA2B I/D polymorphism was performed in 213 individuals: 75 SSS-patients, 49 their healthy relatives, 89 healthy volunteers.Results. 3 types of ADRA2B genotypes (II — homozygous wild, ID — heterozygous, DD — homozygous mutant) were founded by allele-specific polymerase chain reaction. Significant prevalence of the homozygous genotype of more rare alleles DD in SSS-patients (28±5.2%) compared to the control group (8.99±3.0%) was found.Conclusion. Study of the genetic marker can be used to identify predisposition to hereditary SSS in the population and individual-family level. SSS due to mutations in genes that regulate cell function of sinus node and the sinoatrial conduct occurs, apparently, extremely rarely.