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The continuing interest in the problem of vibration disease (VD), especially when combined with arterial hypertension (AH), is due to the steady development of industrial sectors associated with vibration acceleration and the tendency towards the early development of AH. Aim of the study was to investigate the features of clinical, nutritional and anthropometric indicators and frequency of occurrence of Ala16Val (rs4880) polymorphic locus of the manganese superoxide dismutase (MnSOD) gene in VD combined with AH. Material and methods. 431 people were examined, among them 104 patients with VD stage I, 101 – with VD stage I in combination with AH I–II stage, 107 – with AH I–II stage, without contact with vibration, and 119 people working at the same enterprise without contact with vibration, without signs of hypertension. A complex of clinical, anthropometric, laboratory, functional and genetic studies has been carried out. Results. In case of VD comorbid with AH, the frequency of complaints, both general and specific, significantly increases compared to other groups. Body mass index, waist circumference / hip circumference (WC/HC) ratio, fat mass increase, extracellular fluid content with a decrease in active cell mass, musculoskeletal mass and phase angle compared with the control group. An imbalance of nutrition in terms of macro- and micronutrients, an increased content of the fat component in the diet with a deficiency in the diet of omega-3 polyunsaturated fatty acids has been established. In persons with VD and AH, the C/C genotype, which is more common in healthy people, is registered in only 16% of cases, while the polymorphic variant T/T is in 29 %, which exceeds the corresponding value in the control and isolated AH groups by 1.9 and 1.5 times, respectively. Discussion. The common pathogenetic features of VD and AH lead to the development of adipose tissue dysfunction and trophological insufficiency. There is no doubt that hypertension is associated with increased body weight, obesity, and adipocytokine serum concentration. An indicator of a high risk of developing cardiovascular pathology, including heart attack, stroke, is an increase in the WC/HC index. The role of the Ala16Val polymorphism of the MnSOD gene in the formation of AH and some variants of occupational diseases has been shown in a number of studies. Conclusions. The variant of VD, comorbid with AH, is characterized by a significant increase in the frequency of detection of the T/T genotype in the polymorphic locus Ala16Val (rs4880) of the MnSOD gene in combination with an altered nutritional and anthropometric status of such patients. The presence of this polymorphism may be associated with an increased risk of developing concomitant vascular pathologies in VD, however, in combination with malnutrition and associated changes in anthropometric parameters, this risk increases many times over. Thus, early diagnosis of the risk of developing comorbid vascular pathology in VD can be aimed at identifying the genotype, and prevention can be aimed at modifying nutrition.

Introduction. A more in-depth description of molecular events that disrupt the functioning of the p53 signaling pathway is important for understanding the mechanisms of formation and progression of diffuse B-large cell lymphoma (DCCL), as well as its sensitivity to treatment. The p53 protein exhibits its oncosuppressive function and mediates the antitumor effects of drugs by regulating transcription and/or maturation of a wide range of target genes, including MIR-34A, MIR34B/C, MIR-129-2 and MIR-203. In the tumor tissue of lymphomas, in comparison with normal lymphoid tissue, a decrease in the level of microRNAs encoded by these genes is shown.Aim. The aim of this study was to conduct a comprehensive analysis of the methylation of the genes of the p53-responsive microRNAs MIR-34A, MIR-34B/C, MIR-203 and MIR-129-2, as well as mutations in the DNA-binding domain and destruction of the polyadenylation signal of the TP53 gene in DLBCL.Materials and methods. 136 DNA samples isolated from tumor tissue of patients with DLBCL and 11 DNA samples obtained from lymph nodes with reactive B-cell follicular hyperplasia were analyzed. The methylation status of MIR-203 and MIR-129-2 genes was determined by the method of methyl-specific polymerase chain reaction, MIR-34A and MIR-34B/C genes by the method of methyl-sensitive analysis of high-resolution melting curves. In tumor samples, rs78378222 genotyping was performed by polymerase chain reaction with restriction fragment length polymorphism, resulting in the destruction of the polyadenylation signal, and the nucleotide sequence of the region of the TP53 gene encoding the DNA-binding domain was determined by capillary direct sequencing by Sanger.Results. The methylation detected in lymphoma tissue was tumor-specific. The frequency of analyzed aberrations in the TP53 gene and methylation of MIR-34A, MIR-34B/C, MIR-129-2 and MIR-203 was 21, 23, 55, 65 and 66 %, respectively. At the same time, methylation of the analyzed genes of p53-responsive microRNAs and aberrations in the TP53 gene in the tumor tissue of patients with DLBCL were independent events with a tendency to mutual exclusion. At the same time, it was shown that in the vast majority of lymphoma samples, the methylation of the MIR-34A, MIR-34B/C, MIR-129-2 and MIR-203 genes was combined.Conclusion. Along with aberrations in TP53, methylation of MIR-34A, MIR-34B/C, MIR-129-2 and MIR-203 genes may be an important cause of decreased expression of miR-34a, miR-34b, miR-34c, miR-129 and miR-203 in DLBCL. The combined methylation of the MIR-203, MIR-129-2 and MIR-34B/C genes, as well as the MIR-34B/C and MIR-34A pairs, potentially has a more pronounced pro-tumor effect due to the presence of common targets in the microRNAs encoded by them.

The study of DNA methylation status in malignant lymphomas is a new field of research in oncohematology. The aim of this study was to quantify the level of methylation of the MIR-143 gene in the tumor tissue of patients with diffuse large B-cell lymphoma (DLBCL). Material and methods. The study included 81 tumor samples of DLBCL (26 of germinal and 55 of non-germinal origin) and 11 biopsies of reactive lymph nodes. To quantify the methylation of the MIR-143 gene, the method of direct bisulfite sequencing by Sanger was used with the calculation of the average level of methylation of the analyzed CpG-sites. Results. The average level of MIR-143 methylation in tumor samples was significantly lower than the values in reactive lymph nodes (64.43 ± 19.92 и 76.27 ± 4.92 %, respectively, p = 0.049), did not depend on the immunohistochemical subtype of the tumor and showed a greater spread of values. In the lymphoma samples, there was predominant hypomethylation of one of the four analyzed CpG-dinucleotides within the boundaries of the analyzed fragment. Conclusion. The data on a change in the pattern of the MIR-143 gene methylation in the tumor tissue of DLBCL were obtained. To establish the role of microRNA in the pathogenesis of DLBCL further studies aimed at clarifying the mechanisms of epigenetic regulation of MIR-143 expression in lymphoma cells and identification of this microRNA targets are required.

Objective: to study associations between personal anxiety (PA) and single nucleotide polymorphism rs2278749 of the ARNTL gene among individuals aged 25–64 years living in Novosibirsk.Material and methods. Under the WHO program “MONICA-psychosocial (MOPSY)”, a random representative sample of the population aged 25–64 years in Novosibirsk was studied (725 men, mean age – 43.4±0.4 years, response – 71.3%; 710 women, mean age – 44.8±0.4 years, response – 72%). The general examination was carried out according to standard methods included in the protocol of the WHO program. To assess PA, a form of Spielberger self-assessment scales was proposed. Every second respondent underwent genotyping of the studied polymorphisms of the ARNTL gene.Results. The C/C genotype of the ARNTL gene was found in the general population in 60.7% of individuals (in 61.2% of men and 60.5% of women); the C/T genotype was found in 34.1% of individuals (in 35.1% of men and 33.5% of women) and the T/T genotype in the general population was found in 5.2% of individuals (in 3.7% of men and 6% women). The probability of PA development among carriers of the CT+TT genotypes of the ARNTL gene was 2 times higher (p

The purpose of the study was to present up-to-date data on the regulation of expression, function in normal tissues and multidirectional activity in the oncogenesis of miR-143/145 microRNAs cluster, as well as to evaluate the possibilities and limitations of the therapeutic use of microRNAs of this cluster in malignant neoplasms. Material and methods. The search for available domestic and foreign literary sources published in PubMed and RSCI databases over the past 10 years has been carried out. 427 articles were found, of which 41 were included in this review. Results. The conservative cluster miR-143/145 is one of the most intensively studied in tumors. Based on the results of the analysis of differential miRNA expression, in vitro experiments in cancer cell lines and in vivo in mouse tumor models, a decrease in miR-143 and miR-145 levels was shown in malignant neoplasms of epithelial origin. Until recently, these miRNAs were considered classical oncosuppressors. The data presented in the review demonstrate that the results of a number of studies taking into account the cellular aspects of microRNA expression contradict this concept. miR-143 microRNA, for example, is known to participate in the metabolic restructuring of the tumor and the activation of neoangiogenesis. It has been shown that the oncosuppressive or pro-oncogenic activity of miR-143 and miR-145 depend on the tissue and cellular context and can be explained by the presence of several regulated targets that have opposite effects on oncogenesis. Taken together, the data obtained suggest the need to exercise caution when choosing the microRNAs of the described cluster for exogenous therapeutic delivery. Conclusion. Further detailed decoding of the mechanisms of miR-143 and miR-145 functioning in various types of tissues and cells, as well as identification of new MRNA targets are necessary for a better understanding of the involvement of these molecules in oncogenesis.

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.

Objective: to study the associations between polymorphic variants of the 5-HTTLPR SNP rs25531 A>G gene and sleep disorders in the open population of the able-bodied population aged 25–44 years in Novosibirsk.Material and methods. A representative sample of the population aged 25–44 years in Novosibirsk was surveyed in 2013–2016 (403 men, mean age – 34±0.4 years, response – 71%; 531 women, mean age – 35±0.4 years, response – 72%). The general examination, included in the WHO MONICA-psychosocial (MOPSY) program was carried out according to standard methods. Sleep disturbance was assessed using the Jenkins scale. Three hundred forty nine (349) people who underwent genotyping were selected from the total sample using the method of random numbers generation.Results. In the studied population aged 25–44 years, 42.8% of respondents gave a negative assessment of their sleep, 39.7% of men and 45.3% of women had sleep disorders (χ2 =11.397; df=4; p0.05).The most common genotype of the 5-HTTLPR SNP rs25531 A>G gene was SLA (43.3%), LALA (26.4%) was on the second place, SS (17.8%) was on the third place, less represented genotypes in our population were LALG (6.9%), SLG (4.4%), LGLG (1.4%) genotypes.Among individuals with the SLA genotype more common was 5–6 hour sleep (55.3%) (χ2 =4.121; df=1; pG gene on serotonin neurotransmission contributes significantly to the etiology of sleep disorders.

Introduction. The recurrence of diffuse large B-cell cell lymphoma in the central nervous system in the vast majority of cases is a fatal manifestation of the disease. The study of the lymphoma mutational profile can improve the accuracy of the prognosis of relapse in the central nervous system and justify the selection of patients for preventive treatment. Aim. To evaluate the mutational profile of cases of diffuse large B-cell cell lymphoma with central nervous system damage in relapse based on the results of our own experiment on high-performance sequencing.Materials and methods. On the Illumina platform, full-exome sequencing of diagnostic samples of diffuse large B-cell cell lymphoma with relapses in the central nervous system was performed. A panel including more than 70 genes was analyzed.Results. Four main groups of genetic events can be distinguished in the group of studied samples, namely: combined mutations in the NF-kB (MYD88, NOTCH1, CD79B, CARD11) and JAK-STAT (PIM1, STAT6) signaling pathways, as well as aberrations in the main oncosuppressor TP53 and chromatin remodeling system genes (ARID1A, KMT2D, EP300, SMARCA4). A recurrent mutation c. 794T>C, p.L265P MYD88 was detected in the study group. Among other findings, mutations in the CIITA and CD58 genes should be noted, which are important in avoiding tumor cells from immune surveillance.Conclusion. Despite the apparent heterogeneity of the mutational profile of diffuse large B-cell cell lymphoma with relapses in the central nervous system, in most cases, tumor cells were characterized by genetic disorders leading to the production of a large number of pro-inflammatory cytokines by malignant lymphocytes, as well as aberrations that reduce immunogenicity and contribute to the avoidance of immune surveillance by the tumor.

Objective: to study the association of the G-174C (rs1800795) polymorphism of the IL-6 gene with depression in an open population of 25–44 year old in Novosibirsk.Patients and methods. In 2013–2016 years we examined 403 men (mean age – 34±0.4 years, response – 71%) and 531 women (mean age – 35±0.4 years, response – 72%) from an open population of 25–44 year old residents of the Oktyabrsky district, Novosibirsk, the sample was representative. Depression was assessed using the MONICA-MOPSY psychosocial questionnaire. Genotyping of the studied gene polymorphisms was carried out in the Laboratory of Molecular Genetic Research of Scientific Research Institute for Therapy and Preventive Medicine, Federal Research Center Institute of Cytology and Genetics, Russian Academy of Sciences, Novosibirsk.Results and discussion. A severe level of depression occurred in 12.8% of the population, among men – in 8.9%, among women – in 15.8%; and moderate level – in 24.5% of the population (among men – 21.3%, among women – 26.9%). The most common in the population was the heterozygous C/G genotype (45.1%), the G/G genotype was observed in 34.6% of the population and, finally, C/C in 20.3% of participants. The most common allele of the IL-6 gene of the G-174C polymorphism (rs1800795) was the G allele in 57.5% of the population, and the C allele in only 42.5%. Among carriers of the G/G genotype of the IL-6 gene, a moderate (39.7%) or severe level of depression (37.3%) prevailed, while there was no depression in the carriers of the C/C genotype of the IL-6 gene (24.2%; χ2 = 10.962; df=4; p=0.027). Carrying the C/G genotype of the IL-6 gene increased the chance of developing a severe level of depression by almost 2.9–3.3 times in comparison with the carriage of the C/C genotype. Among carriers of the G/G genotype of the IL-6 gene, a severe level of depression was 3.3 times more common than in carriers of the C/C genotype. Individuals carrying the G allele of the IL-6 gene were 1.6 times more likely to experience a severe level of depression than those carrying the C allele.Conclusion. The data obtained suggest that the carriage of the G allele of the G-174C polymorphism (rs1800795) of the IL-6 gene may be associated with a severe level of depression.

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.

BACKGROUND: The prevalence of Type 2 diabetes mellitus (T2DM) has reached epidemic proportions and it is estimated to affect over 400 million people worldwide. Moreover, the incidence of diabetes is expected to continue to rise and it is projected to affect nearly one of the three individuals by the year 2050. These alarming projections suggest that there is an urgent need for the development and implementation of novel prevention and treatment strategies to combat the rise in T2DM.AIM: To study the possibility of using polymorphisms of genes SLC30A8 and MC4R as markers for predicting the development of T2D in the population of Novosibirsk.MATERIALS AND METHODS: On the basis of prospective follow-up of a representative population sample of residents of Novosibirsk (The HAPIEE Project), 2 groups were formed according to the “case-control” principle (case — people who had diabetes mellitus 2 over 10 years of follow-up, and control — people who did not developed disorders of carbohydrate metabolism). T2D group (n = 443, mean age 56.2 ± 6.7 years, men — 29.6%, women — 70.4%), control group (n = 532, mean age 56.1 ± 7.1 years, men — 32.7%, women — 67.3%). DNA was isolated by phenol-chloroform extraction. Genotyping was performed by the method of polymerase chain reaction with subsequent analysis of restriction fragment length polymorphism, polymerase chain reaction in real time. Statistical processing was carried out using the SPSS 16.0 software package.RESULTS: Genotype TT rs13266634 of the SLC30A8 gene was associated with the risk of developing T2D (relative risk — RR 1.51, 95% confidence interval — CI 1.11–2.05, p =0.008). The CC genotype rs13266634 of the SLC30A8 gene was associated with a protective effect against T2D (RR 0.57, 95% CI 0.35–0.92, p=0.026). No significant effect of rs17782313 of the MC4R gene on the risk of developing T2D was found.CONCLUSION: The rs13266634 polymorphism of the SLC30A8 gene confirmed its association with the prognosis of the development of T2D, which indicates the possibility of considering it as a candidate for inclusion in a diabetes risk score. The association between polymorphisms rs17782313 of the MC4R gene and the prognosis of the development of T2D was not found.

The purpose of the study was to present up-to-date data on the frequency and significance of a number of p53-responsive oncosuppressive micrornas genes methylation in malignant neoplasms of the blood system.Material and methods. The search for available literary sources published in the Pubmed and RISC databases was carried out. A total of 399 articles were found, of which 62 were included in this review.Results. The p53 protein regulates a whole class of microRNAs – highly conserved small RNA molecules that affect gene expression mainly by suppressing translation. МicroRNAs play an important role in all cellular processes and can have both oncosuppressive and pro-oncogenic properties. Impaired expression of p53-activated oncosuppressive micrornas in various tumors may be associated with specific epigenetic mechanisms (DNA methylation and histone deacetylation). The review examines the molecular and genetic characteristics of oncosuppressive micrornas functioning in normal hematopoiesis, the violation of expression of which is shown in the development of hemoblastoses, namely: miR-34a, miR-34b/c, miR-145, miR-143 and miR-203. It is known that the transcription of the genes of these microRNAs is carried out and regulated from their own promoters. The latest published research results on the diagnostic, prognostic and clinical significance of gene methylation of the microRNAs under consideration in malignant neoplasms of the blood system are presented. According to literature data, common targets for mir-34a, mir-34b/c, mir-145, mir-143 and miR-203 microRNAs are mRNAs of a number of pro-oncogenes, namely: transcription factor C-MYC, positive cell cycle regulators at the G1/S transition point of CDK4, CDK6 and CYCLIN-D1 phases, anti-apoptotic proteins MDM2, MDM4, BCL2 and MCL1, as well as DNMT3A and DNMT3B methyltransferases and other molecules. In this regard, it should be noted that there are positive feedbacks between p53 and microRNAs activated by it, as well as negative feedbacks between p53-responsive micrornas and C-MYC and DNA methyltransferases.Conclusion. Thus, the data presented in the review clarify the current understanding of the work of the regulatory network of the p53 protein and the micrornas activated by it, and also emphasize the functional association of p53-responsive microRNAs.

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.

Aim. To investigate polymorphisms of 18 genes as possible molecular genetic markers of predisposition or resistance to development of non-infective (NE) or infective endocarditis (IE).Materials and methods. The study encompassed 81 patients with NE and 94 patients with IE. The control group included 225 conditionally healthy people. Polymorphisms of 18 genes were tested using polymerase chain reaction (PCR).Results. For the first time, a statistically significant relationship was identified between gene polymorphisms and valvular vegetations: for genes in the hemostatic system – rs6025 (1691 G > A) of the F5 gene (AG genotype), rs1126643 (807 C > T) of the ITGA2 gene (TT genotype); for folate pathway genes – rs1805087 (2756 A > G) of the MTR gene (AG genotype) and rs11697325 (–8202 A/G) of the MMP9 gene (AA genotype) and rs2476601 (C1858T) of the PTPN22 gene (TT genotype). The protective effect of gene polymorphisms was revealed: for the NOS3 gene (4b / 4b genotype) and G (–572) C of the IL6 gene (CC genotype). For two polymorphisms, an association with thromboembolic complications in NE was revealed: rs1126643 (807 C > T) of the ITGA2 gene and rs1799889 (–675 5G > 4G) of the PAI (SERPINE1) gene. In IE, such an association was detected for the polymorphism rs11697325 (–8202 A/G) of the MMP-9 gene.Conclusion. The polymorphisms of candidate genes were revealed, that are associated with the clinical and hemostasiological characteristics of IE and NE. In NE, for the first time, the association with thromboembolic complications was identified for two polymorphisms: rs1126643 (807 C > T) of the ITGA2 gene and rs1799889 (– 675 5G > 4G) of the PAI-1 (SERPINE1) gene. In IE, such a relationship was detected for one polymorphism – rs11697325 (8202 A/G) of the MMP-9 gene.

The study of sudden cardiac death (SCD) and its etiopathogenesis in cardiology practice remains one of the most pressing public health problems. In Western countries, SCD accounts for 20% of the total mortality and 50% of mortality associated with cardiovascular diseases. Considering the electrical instability in the myocardium as one of the main reasons for the development of life-threatening arrhythmias (ventricular tachycardia / ventricular fibrillation) and SCD, one should be aware of such provoking factors as ischemic heart disease, myocarditis, valvular heart disease, pharmacological influences, cardiomyopathy, and channelopathy. An increase or decrease in the duration of the QT interval, which reflects the work of ion channels, as well as ventricular depolarization and repolarization, increases the risk of SCD.The aim of this review was to study and analyze the available literature data on the relationship of molecular genetic markers with the duration of the QT interval.Currently, there is a number of genetic studies that allow to identify a large number of mutations and polymorphisms of known genes that affect the variability of the QT interval, showing their significance in risk stratification of sudden arrhythmic death and choosing the right tactics for managing, preventing, and treating patients, thus reducing the risk of SCD. The predictive value of genetic testing is the highest for long QT syndrome (LQTS), for which a gene-specific risk profile has been established, and lower for other channelopathies. A large amount of genetic data may be a promising approach to quantifying the risk of SCD, especially at a young age, which will be facilitated by further study of this problem.

BACKGROUND: «The vicious circle» of associations of diabetes mellitus (DM) with pancreatic pathology, when pancreatic diseases can initiate DM, and type 2 DM — cause functional and organic pancreatic pathology, determines the search for possible associations. Some studies have established a relationship between TNF or TP53 polymorphisms with DM or with pancreatic diseases.AIMS: to determine and compare fasting plasma glucose and the frequency of hyperglycemia in patients with acute pancreatitis (APp), chronic pancreatitis (CPp), pancreatic cancer (PCp) depending on gender, etiology or stage of the disease, polymorphism -308G/A TNF gene in all patients, and polymorphism 72Arg/Pro gene TP53 in PCp..MATERIALS AND METHODS: At the observational multicenter clinical cross-sectional uncontrolled case-study 44 APp, 97 CPp and 45 PCp were examined; the groups were comparable by sex/age. Informed consent form for participate in the study was obtained from all patients. The main outcome of the study: frequency of hyperglycemia in APp, CPp, PCp, considering the polymorphism TNF and TP53 genes. RESULTS: The lowest age-standardized fasting plasma glucose (FPG) was found in CPp (6,2±0,2 mmol/l) than in APp (6,7±0,2 mmol/l, p=0,041). In PCp (6,6±0,2 mmol/l), the average levels of FPG did not differ substantially when compared with APp (p=0,749) or CPp (p=0,092). In APp, the norm of GP was detected less frequently (31,8%) than in CPp (54,6%, χ2 =6,3, p=0,012), and the frequency of the norm of GP in PCp (48,9%) did not differ with that in APp or CPp. The frequency of FPG≥6,10,05. In PCp genotypes Arg/Arg, Arg/Pro, Pro/Pro polymorphism gene 72Arg/Pro TP53 in 2,4, 35,7, 61,9% of cases. No associations of GP≥7,0 mmol/l with TNF polymorphism in APp, CPp, PCp and with TP53 polymorphism in PCp were obtained.CONCLUSIONS: The frequency of FGP≥7,0 mmol/l did not differ for various pancreatic disease and was not associated with the risk of pancreatic necrosis and “defined” CP. The -308G/A polymorphism TNF gene did not differ in APp, CPp or PCp and was not associated with impaired carbohydrate metabolism. The 72Arg/Pro polymorphism TP53 gene in PCp was not associated with impaired carbohydrate metabolism.

The objective of the study: to study rs2227983 polymorphism of EGFR gene in patients with allergic asthma and healthy individuals.Subjects and Methods. 179 patients suffering from allergic asthma were included in the study. The diagnosis and degree of severity were established in accordance with the GINA recommendations. The Control Group included apparently healthy individuals (n = 217). Patients with allergic asthma underwent standard laboratory and instrumental examinations and DNA typing.Results. A statistically significant predominance of AG genotype frequency in the group of patients with allergic asthma, including women, versus the group of healthy individuals, was established. AG rs2227983 genotype of EGFR gene was found to be significantly more common in patients with mild and moderate allergic asthma including women, than in healthy individuals, including women.Conclusion. The association of rs2227983 polymorphism of EGFR gene with allergic asthma has been established. A homozygous GG genotype may play a protective role against the disease.

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.

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.

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.

Objective: to investigate the association of the polymorphic marker Val158Met in the catechol-O-methyl transferase (COMT) gene with depression in an open population aged 25–44 years.Patients and methods. A representative sample of the population living in Oktjabr'skij district of Novosibirsk aged 25– 44 years (427 men, median age – 34±0.4 years, response rate – 71%; 548 women, median age 35±0.4 years, response rate – 72%) was screened in 2013–2016 (budget framework № 0324- 2018-0001, Reg. № AAAA-A17-117112850280-2). In addition to the standard epidemiological examination, screening participants underwent psychological testing, which determined the level of depression. Study participants who underwent COMT Val158Met (rs4680) polymorphism genotyping were randomly assigned to a cohort of 224 men and 217 women. Pearson's χ2 test was used to test the statistical significance of differences between these groups; p≤0.05 was considered statistically significant in all types of analysis. Results and discussion. In an open population aged 25–44 years, the prevalence of severe depression (SD) was 13.2%, moderate depression – 24.4%. SD was more prevalent in COMT G/G genotype carriers (61.8%), compared to A/A genotype carriers (38.2%; χ2=6.097; df=2, p=0.047); the G allele carriers also had a higher prevalence of SD (55.3%), compared to A allele carries (44.7%; χ2=5.408; df=1; p=0.02). SD was less prevalent among male COMT A/A genotype carriers (15.8%), compared to G/A genotype carriers (84.2%; χ2=4.603; df=1; p=0.032). SD was more prevalent in female G/G genotype carriers (65.5%), compared to A/A genotype carriers (34.5%; χ2=4.769; df=1; p=0.029). The G allele was more common among women with SD (58.2%) than the A allele (41.8%; χ2=6.658; df=2; p=0.01). In a logistic regression model, COMT Val/Val genotype in the studied population [Relative risk (RR) 1.594], as well as G (Val) allele in the studied population (RR=1.378) and women (RR=1.557), significantly increased the risk of depression. Conclusion. The data allows us to assume that COMT G/G polymorphism may be linked to a high depression level.

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.

Background. The annual reporting forms for malignant neoplasms do not provide for the division of lymphomas into variants. In international publications and statistical reference books of the Russian Federation, variants of non-Hodgkin’s lymphomas (NHL) are also not separated. For these reasons, a detailed assessment of the epidemiology of NHL in Russia is difficult, and data for individual variants of the disease are not provided.Purpose: to present the clinical and epidemiological characteristics of Diffuse Large B-cell Lymphoma (DL BCL ) in Novosibirsk according to the data of the City Hematology Center (CHC).Material and Methods. A retrospective analysis of primary medical documentation (case histories, outpatient charts, and immunohistochemical study reports) of 271 patients with DL BCL was performed in the period from January 1, 2013 to December 31, 2018.Results. The calculated registered primary morbidity and mortality from DL BCL in Novosibirsk for the analyzed years fluctuated slightly. The average incidence and mortality rates were 2.85 and 1.98 per 100,000 population, respectively. When analyzing the dynamics of the prevalence of DL BCL in Novosibirsk, a positive trend of annual increase in the indicator was revealed: 1.87 times over the past 6 years. In men, the tumor developed 2.6 years earlier than in women. In General, the risk of getting DL BCL after 50 years was 3 times higher than at the age of 30 years. Among patients diagnosed with primary lymphoma who underwent treatment at the Hematology department of CHC, half of the patients had DL BCL .Evaluation of the clinical characteristics showed a pronounced severity of the analyzed cohort.Conclusion. The updated quantitative and qualitative indicators of clinical and epidemiological characteristics of DL BCL in Novosibirsk for 2013–18 were obtained. These indicators can be used for further monitoring, development and implementation of measures for the prevention, diagnosis and treatment of this form of hemoblastosis.

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.

Aim. A study of the association of the methylation of the promoter of the ABCA1 gene with sudden cardiac death(SCD).Materials and methods. The study design is based on the case-control principle. The SCD group included 150 men (mean age (46.7 ± 9.2) years) who died of sudden cardiac death according to forensic medical examination data (the main pathological diagnoses are acute circulatory failure, acute coronary insufficiency). The control group included 150 men (mean age (42.6 ± 1.2) years) who died suddenly, but not due to cardiovascular pathology. DNA was isolated by phenol-chloroform extraction from myocardial tissue. The methylation status of the ABCA1 gene promoter was assessed by methyl-specific polymerase chain reaction. The results obtained were statistically processed in SPSS 16.0 using Pearson’s test and Fisher’s test with Yates’ correction for continuity. P < 0.05 was used as a level of significance.Results. Comparing the groups revealed statistically significant differences in the methylation status of the gene promoter (p = 0.015). In the SCD group, the proportion of individuals whose ABCA1 gene promoter is methylated is statistically significantly higher compared to the control group (p = 0.020; OR = 5.86; 95% CI (1.28–26.89)).Conclusion. Methylation of the promoter of the ABCA1 gene is associated with sudden cardiac death.

Aim.To study the association of single-nucleotide polymorphismrs3025058(5а/6а) with the development of stroke in patients of the East Siberian population with cardiovascular pathology and risk factors for its development. Materials and methods.The study involved 260 patients with stroke (age [57.0; 51.062.0]) and 272 patients of the control group (age [55.0; 51.062.0]). Among the patients who underwent stroke, 157 men and 103 women. The control group included 170 men and 102 women. The examination of the main group included: collection of complaints, anamnesis, clinical examination, computed tomography of the brain, electrocardiography, echocardioscopy, ultrasound duplex scanning of the extracranial brachiocephalic arteries, 24-hour monitoring of blood pressure and heart rate, analysis of the blood coagulation system. The patients of the main group had the following cardiovascular pathology and risk factors: arterial hypertension, paroxysmal supraventricular tachycardias, dyslipidemia, atherosclerosis of extracranial brachiocephalic arteries, disorders of the hemostasis system. The control group was examined within the framework of the international project HAPIEE. Molecular genetic research was carried out by real-time PCR. Statistical processing of the material was carried out using the Statistica for Windows 7.0, Excel and SPSS 22 application software. Results.The study established statistically significant associations between the 5a/5a genotype and the 5a allele and stroke in the general group of patients, as well as in the subgroup of men, subgroups of patients with extracranial brachiocephalic arteries atherosclerosis and dyslipidemia. In the subgroup of patients with cardiac arrhythmias, statistically significant results were obtained only for allele 5a, and in the subgroup of women with stroke, subgroups of patients with arterial hypertension and hypercoagulation, no significant associations ofrs3025058(5a/6a) polymorphism with stroke were found. Conclusion.Genotype 5a/5a and allele 5a of the single-nucleotide polymorphismrs3025058(5а/6а) increase the risk of stroke in individuals from the East Siberian population, including those in the presence of such risk factors as extracranial brachiocephalic arteries atherosclerosis and dyslipidemia.

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.

Aim.To study the possibility of using polymorphisms of genesTCF7L2,FABP2,KCNQ1,ADIPOQas markers for predicting the development of type 2 diabetes mellitus (T2D) in the population of Novosibirsk. Materials and methods.On the basis of prospective observation of a representative population sample of residents of Novosibirsk (HAPIEE), 2 groups were formed according to the case-control principle (case people who had diabetes mellitus 2 over 10 years of observation, and control people who did not developed disorders of carbohydrate metabolism). T2D group (n=443, mean age 56.26.7 years, men 29.6%, women 70.4%), control group (n=532, mean age 56.17.1 years, men 32.7%, women 67.3%). DNA was isolated by phenol-chloroform extraction. Genotyping was performed by the method of polymerase chain reaction with subsequent analysis of restriction fragment length polymorphism, polymerase chain reaction in real time. Statistical processing was carried out using the SPSS 16.0 software package. Results and discussion.No significant effect of rs1799883 of theFABP2gene, rs2237892 of theKCNQ1gene, and rs6773957 of theADIPOQgene on the risk of developing T2D was found. Genotypes TT and TC rs7903146 of theTCF7L2gene are genotypes for the risk of developing T2D (relative risk RR 3.90, 95% confidence interval CI 2.316.61,p0.001; RR 1.86, 95% CI 1.422.43,p0.001, respectively). The CC genotype rs7903146 of theTCF7L2gene is associated with a protective effect against T2D (RR 0.37, 95% CI 0.290.49,p0.001). When theTCF7L2gene is included in the model for assessing the risk of developing T2D rs7903146, it retains its significance in both men and women. Conclusion.The rs7903146 polymorphism of theTCF7L2gene confirmed its association with the prognosis of the development of T2D, which indicates the possibility of considering it as a candidate for inclusion in a diabetes risk meter. Variants of risk meters have been developed to assess the prognosis of the development of diabetes mellitus 2 in men and women aged 4569 years during 10 years of follow-up. The association with the prognosis of the development of T2D polymorphisms rs1799883 of theFABP2gene, rs2237892 of theKCNQ1gene and rs6773957 of theADIPOQgene was not found.

Background. The problem of studying the development of stroke in men of working age working in conditions of high professional risk is relevant. Aim of the research. To develop a method for predicting the development of stroke in men working under conditions of exposure to toxic dust factors. Materials and methods. The study included 111 men aged 30 to 65 years who worked for 5 or more years in the following professions: electric gas welder, gas welder, smelter. The study participants were divided into two groups: the first group – 45 men who had a stroke; the second group – 66 men who did not have stroke history. The subjects of both groups were comparable in terms of occupational structure, age and length of service. Using the method of sequential inclusion of the studied risk factors for stroke development (Forward Stepwise), we determined those that made a significant contribution to the possible development of stroke. Results. Based on multivariate analysis, a logistic regression formula was derived that determines the likelihood of a stroke in patients working under the influence of the toxic dust factor, which included the following factors: the presence of dyslipidemia factor (β-coefficient = 3.7; p = 0.001), the patient’s diagnosis is “stage III arterial hypertension” (β-factor = 5.6; p = 0.002), blood pressure control (β-factor = –3.4; p = 0.005). The patient determines the value of these three parameters, substitutes the appropriate formula for calculating the value of p(X). A value of p(X) in excess of 0.5 indicates a high risk of stroke in men working under conditions of exposure to toxic dust factors. The sensitivity of the proposed method was 84.4 %, specificity – 92.4 %. Conclusion. The multivariate model is informative for the individual prediction of the development of stroke in men working under the influence of the toxic-dust factor, since it reflects the degree of influence of one or another factor on the development of the disease.

The aim of the study was to investigatey the association of single-nucleotide polymorphism (SNP) rs10507391 (A>T) with the acute cerebrovascular accident (CVA) development in patients of the East Siberian population with cardiovascular pathology and its risk factors.Material and methods. The study involved 260 patients with acute CVA (age [57.0; 51.0–62.0]) and 272 patients of the control group (age [55.0; 51.0–62.0]). Among the patients who had acute CVA there were 157 men and 103 women. The control group included 170 men and 102 women. The examination of the experimental 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, and 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 tachycardias, dyslipidemia, atherosclerosis of the brachiocephalic arteries, and disorders of the hemostatic system. The control group was surveyed in the framework of the international “HAPIEE” project. Molecular genetic research was performed by real-time PCR. Statistical processing of the material was carried out using the following software: Statistica for Windows 7.0, Excel and SPSS 22. Results. When studying the association of SNP rs10507391 (A>T) with the acute CVA development in all the analyzed groups and subgroups of patients, a link was established between the rare TT genotype and the T allele and an increased risk of acute CVA.Conclusion. TT genotype and T allele of the SNP rs10507391 (A>T) increase the risk of acute CVA in patients regardless of previous cardiovascular pathology and its risk factors, including patients with arterial hypertension, supraventricular tachyarrhythmias, atherosclerosis of brachiocephalic arteries, impaired lipid metabolism and hemostasis system.

Objective: to study the association of hostility with high and low-active variants of the MAOA gene in an open population of men 45-64 years old. Using the methods proposed by the WHO International Program “MONICA-psychosocial” and “HAPIEE”, a representative sample of men aged 45–64 years old (n = 781 men, average age was 56.48 ± 0.2 years) in 2003-2005. All respondents independently completed a questionnaire on hostility. From the surveyed sample, using the random number method, 156 men were selected who were genotyped for MAOA-uVNTR polymorphism. It was approved that the level of hostility in the population of men was 60.3%. It was revealed that among persons with low-active alleles of the MAOA-L gene (allele 2 and 3) a high level of hostility was more common — 50.9%. The results of building a logistic regression model showed that the presence of low-active alleles (2; 3) of the MAOA gene increases the likelihood of hostility OR = 2,103 (95% CI 1,137-3,889, p = 0.018). The results obtained allow us to conclude that the low-active allele of the MAOA-L gene is associated with hostility.

Background. the presence of functionally significant intron mutations in the TP53 gene was demonstrated in experiments in vitro and on samples of patients with some variants of non-Hodgkin’s lymphomas. to date, the studies of TP53 in tumor tissue of patients with diffuse large B-cell lymphoma (dlBCl) have been focused on the mutations in 5–8 exons of the gene. For these reasons, further studies of the spectrum of changes in the intron sequences of the TP53 gene and the determination of their functional effect in dlBCl are required.Description. We present two case reports that are of interest as the cases for detection of functionally significant intron TP53 mutations in dlBCl tissue, first published in the Russian scientific literature. the first clinical case of dlBCl was clinically characterized by extranodal tumor at the onset of the disease, severe symptoms of tumor intoxication, high paraclinical tumor activity, and early hemoblastosis recurrence. the second case of dlBCl was characterized by initially massive tumor lesion, rapidly progressive course of the disease, severe symptoms of tumor intoxication, high paraclinical tumor activity and poor response to therapy with subsequent generalization of lymphoma. Conclusion. Mutations in the TP53 gene are the driver of the tumor process, serve not only as a marker of aggressive tumor progression, but also as an independent predictor of reduced sensitivity to treatment. the presented clinical cases show that an in-depth analysis of the results of the TP53 sequencing in tumors and functional assessment of all detected changes, including changes in the introns of the gene and involving in silico analysis techniques, are necessary.

The primary objective of personalized vaccination is to induce an efficient immune defense while avoiding excessive immunization. Hence, it necessitates the development of methods for predicting the magnitude of the immune response prior to vaccination. Telomere length can be considered as a promising prognostic parameter for assessing the immune response to vaccination. The aim of the work was to analyze the possible association between leukocyte telomere length and specific antibody levels after vaccination against tick-borne encephalitis. The study included 55 men and 40 women who had not previously been vaccinated against tick-borne encephalitis and had no contacts with ticks. Vaccination was carried out with the EnceVir vaccine. One month after vaccination, the level of specific IgG antibodies against tick-borne encephalitis virus was analyzed using the VektoVKE-IgG-strip test system and leukocyte telomere length was measured using real-time quantitative PCR. According to the intensity of vaccine-elicited immune responses, patients were divided into three groups: unresponsive (IgG level 0–100 IU/ml), slightly responsive (IgG level 101–200 IU/ml) and highly responsive (IgG level above 200 IU/ml). The telomere length, at least at trend level (p < 0.1), correlated with the response to vaccination as well as age, educational level and the presence of emotional stress. Using a general linear model, an association between telomere length and immune response to vaccination against tick-borne encephalitis at trend level (p < 0.1) was found only in women. Using a pairwise comparison, it was found that telomere length was significantly higher in highly responsive women than in unresponsive women. Hence, an association between leukocyte telomere length and specific antibody levels after vaccination against tick-borne encephalitis was identified in women. Therefore, peripheral blood leukocyte telomere length can be considered as a promising marker for predicting lymphocyte proliferative responses and the magnitude of vaccine-elicited cellular immune responses.

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.

Objective: to study the association of the polymorphic genotypes of rs4680 in the catechol-O-methyl transferase (COMT) gene with vital exhaustion (VE) in a 45–64-year-old population. Patients and methods. A representative sample of a 45–64-year-old population (781 men and 869 women) was surveyed within screening IV of the international Health, Alcohol and Psychological Factors in Eastern Europe (HAPIEE) program and the WHO MONICA-psychosocial program in 2003-2005. All the study participants filled out a VE scale of the WHO MONICA-psychosocial program. COMT Val158Met (rs4680) polymorphism was genotyped. Pearson' χ2 test was used to test the statistical significance of differences between these groups. The statistical significance level was taken to be p≤0.05 in all types of analysis. Results and discussion. Heterozygous G/A polymorphism in the COMT gene was most common in both the general population (48.6%) and men (44.4%) and women (51.5%). In the general population, the A/A genotype was more common in individuals with a high VE (HVE) level; in women and men, it was detected in 13.3 and 30.8% of cases, respectively. The G/G genotype prevailed in individuals with moderate VE in both the general population (31.1%) and women (29.7%) and men (33.3%). Conclusion. In the general population, the A/A genotype was found to be more common in individuals with HVE (18.6%), in women (13.3) and in men (30.8%).

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.