Abstract: Aim. To study the association of single nucleotide polymorphism (SNP) rs556621 (G 〉 T) with the development of stroke in patients of the East Siberian population with cardiovascular pathology and risk factors. Material and methods. The study involved 260 patients with stroke (157 men and 103 women) and 272 patients of the control group (170 men and 102 women). The following cardiovascular pathology and risk factors were present in the patients of the main group: arterial hypertension, paroxysmal supraventricular tachycardias, dyslipidemia, atherosclerosis of the brachiocephalic arteries, disorders of the hemostatic system. All patients underwent clinical, instrumental and molecular genetic examination. Statistical processing of the material was carried out using the set of application programs Statistica for Windows 7.0, Excel and SPSS 22. Results. As a result of the study, no statistically significant associations of genotypes and alleles of the rs1800801 polymorphism (C 〉 T) with stroke were found in any of the analyzed groups and subgroups. Conclusion. SNP rs1800801 (C 〉 T) does not have a significant effect on the development of stroke in people of the East Siberian population, regardless of the preceding cardiovascular pathology and risk factors.

Abstract: Aim. Research the relationship of gene polymorphisms (MTHFR, FGB, F2, F5) with the development of pulmonary embolism (PE). Material and methods. The study involved 120 people (main group) who underwent PE. Mean age is 63.223.16 years (66 men, mean age 60.243.17 years; 54 women, mean age 66.193.67 years). The control group was composed of Research Institute of Internal and Preventive medicine (Novosibirsk) DNA bank (comparable to the main group by gender and age). This DNA bank was formed during a series of population-based screening. The material for the study includes whole blood, plasma and serum samples, DNA samples, as well as medical records of patients undergoing PE. DNA extraction from venous blood was performed by the phenol-chloroform method. FGA (Del/Ins) rs35496957 was genotyped using polymerase chain reaction (PCR) with flanking primers-8202 A/G, rs11697325 mmp9 using PCR with RFLP. Polymorphisms of genes MTHFR, FGB, F2, F5 were tested by real-time PCR on test systems produced by DNA-technology (Russia) on a DTPrime device (Russia). For structuring and statistical data processing Microsoft Excel and the Microsoft Office software package and the STATISTICA (USA) software package for statistical analysis were used. The study includes the calculation of the following output data and parameters based on the collected incoming statistical data: standard deviation, calculating the mean square value, Pearson's chi-square, likelihood ratios, Fisher's exact test and linear-by-linear association. Results. It was found that the odds ratio of developing PE in men carriers of the TT genotype of the C677T polymorphism of the MTHFR gene at the age of 65 years and older was 4.43 times higher than in carriers of the other two genotypes (95% confidence interval 1.3314.73; p=0.019). There was a tendency of more frequent detection of the genotype GG polymorphism rs1800790 (-455 GA) of the FGB gene among men individuals of the main group compared with the control group (63.6 and 54.0%, respectively). There was also a decrease in the number of respondents with the AA genotype of the rs1800790 polymorphism (-455 GA) of the FGB gene in the group of both genders. There was a tendency of more frequent PE cases among women individuals with genotype GG and GA of the rs1799963 polymorphism of the F2 gene in the main group (85.20 and 14.80%, respectively). Conclusion. Further research of genetic factors role in the occurrence of PE is extremely important for clinical practice taking into consideration the possibility of developing a personalized approach to treatment and prevention of the diseases related to disorders in the hemostatic system.

Abstract: Background. Atrial fibrillation (AF) is the most common type of heart rhythm disturbance, leading to the development of lifethreatening conditions, such as cardio embolism, heart failure, and even sudden cardiac death. In recent years, the genetic aspects of AF have been actively discussed. The largest number of genetic predictors of AF was identified after a full genome-wide association studies (GWAS). Given that so far no studies of the association of rs10824026 polymorphism of chromosome 10q22 with the development of AF have been conducted in the Russian population, we conducted this clinical study. Aim. Checking the associations of the development of AF with the single-nucleotide polymorphism rs10824026 of the SYNPO2L gene in the East-Siberian population. Materials and methods. The study design was formed in accordance with the National Standard of the Russian Federation Good Clinical Practice, GOST P 52379-2005. The study uses design - “case-control”. The main group of patients - patients with known cardiac arrhythmias by the type of AF (n=106, average age 57.0±9 years, men 49.4%, women 50.6%), the group was formed using the criteria of the World Health Organization and the European Society of cardiologists. The control group (n=105, average age 57.0±9 years, men - 50.0%, women - 50.0%) was selected by age and gender from the DNA bank of international studies MONICA (Multinational MONItoring of trends and determinants in cardiovascular disease) under a joint agreement with the Research Institute of Therapy and preventive medicine - Novosibirsk. DNA was isolated by phenol-chloroform extraction. Among other things, among the research methods, routine laboratory methods were used; instrumental data; and invasive tactics such as CAG. Results. As a result of clinical genetic testing, it was found that the frequency of G/G polymorphism of the SYNPO2L gene in patients with AF shows a statistically significant difference.

Abstract: Aim. To study the association of rs662799 gene APOA5 with the development of Acute Cerebrovascular Event in patients with cardiovascular diseases (CVD) and their risk factors. Material and methods. 260 Acute Cerebrovascular Event patients (main group) and 272 control group patients were examined. The age range of patients of the main group is defined from 32 to 69 years [57.0; 51.062.0], individuals in the control group were 37 to 68 years old [55.0; 51.062.0] . The distribution by sex of the main group was as follows: 157 men (age [56.5; 51.062.0]) and 103 women (age [57.0; 51.062.0] ). The sex and age composition of the control group is comparable to those of the main group: 170 men (age [55.0; 51.062.0]) and 102 women (age [55.0; 51.062.0] ). The main group's research methods were as follows: clinical examination, computed brain tomography, electrocardiography, echocardioscopy, ultrasound duplex scanning extracranial brachiocephalic arteries, daily monitoring of blood pressure and heart rate, blood coagulation system analysis. The control group of our study is a population sample of residents of Novosibirsk, who were examined according to the standard of the international HAPIEE project. Examination of individuals in the control group included: questionnaire (socio-economic living conditions, chronic diseases, level of physical activity, mental health), anthropometry (height, weight, waist volume, hips), survey on smoking, alcohol consumption (frequency and typical dose), blood pressure measurement, lipid profile assessment, stress angina detection (Rose) survey, resting electrocardiogram in 12 leads. All patients of the main and control groups underwent molecular genetic analysis of venous blood. Statistical processing of the material was carried out using the set of applications Statistica for Windows 7.0, Excel and SPSS 22. Results. 199 patients (123 men and 76 women) of the main group had ischemic stroke, 51 patients (28 men and 23 women) were diagnosed with hemorrhagic stroke, 10 patients (6 men and 4 women) showed a mixed type of Acute Cerebrovascular Event. Of the 260 patients, 19 (13 men and 6 women) had repeated Acute Cerebrovascular Event. None of the patients examined had clinical, anamnestic and instrumental evidence suggesting the presence of CVD. The most common CVD preceding Acute Cerebrovascular Event was arterial hypertension AH (249 people, 153 of them men and 96 women). Heart rhythm disorders by type of paroxysmal supraventricular tachycardia, including atrial fibrillation, were detected in 31 patients (20 men and 11 women). Among the risk factors for Acute Cerebrovascular Event in the patient group surveyed, dyslipidemia was observed (159 patients, 95 men and 64 women), atherosclerosis of brachiocephalic artery (160 patients, 94 men and 66 women), disorders of the hemostasis system towards hypercoagulation (90 patients, 53 of them men and 37 women), 28 patients (19 men and 9 women) had an aggravated hereditary history according to Acute Cerebrovascular Event. In the control group, AH was diagnosed in 177 patients, of which 98 were men and 79 were women. Other CVD and their risk factors were absent in the control group at the time of the survey. The statistically significant prevalence of rare GG genotype and G allele wearability among Acute Cerebrovascular Event patients compared to healthy patients was verified (4.7% of patients in the main group versus 0.4% in the control group; p=0.001). In addition, a statistically significant decrease in the number of carriers of the advanced AA genotype and allele A compared to the control group (61.8% in the main group versus 61.5% in the control group, р=0.000) was determined in patients with Acute Cerebrovascular Event. In the subgroup of men with Acute Cerebrovascular Event, the common AA genotype was statistically significantly less common (59.9%) than among men in the control groups (82.9%; р=0.000; odds ratio OR 3.26, 95% confidence interval СI 1.955.46). The AG genotype was significantly predominant in the subgroup of men with Acute Cerebrovascular Event (33.6%), than in the control group of men (17.1%; р=0.001). A rare GG genotype was detected in 6.6% of men with Acute Cerebrovascular Event, and among men in the control group, this genotype was absent (р=0.001). In the subgroup of women with Acute Cerebrovascular Event, the AG genotype was statistically more common (33.3%) than among women in the control group (14.7%; р=0.002). The AA genotype, in contrast, significantly predominated in the control subgroup of women (84.3%) compared to women with Acute Cerebrovascular Event (64.7%; р=0.001; OR 2.93, 95% СI 1.495.75). No statistically significant differences were obtained with respect to the GG genotype. Thus, in the subgroup of women with Acute Cerebrovascular Event, the GG genotype of ONV rs662799 (AG) occurred in 2.0% of patients, in the control subgroup of women in 1.0% (р=0.56). We analyzed the frequencies of the genotypes and alleles rs662799 (AG) of the APOA5 gene among patients with AH undergoing Acute Cerebrovascular Event and individuals in the control group without AH and Acute Cerebrovascular Event. The frequency of the AA genotype in the subgroup of AH patients undergoing Acute Cerebrovascular Event was 62.1%, in the control group 78.9% (р=0.003; OR 2.28, 95% CI 2.135.98). The AG genotype was detected in 33.7% of patients with AH and Acute Cerebrovascular Event and in 21.1% of individuals in the control group (р=0.022). The GG genotype in the subgroup of patients with AH and Acute Cerebrovascular Event occurred at a frequency of 4.1%, was absent in the control group (р=0.045). In the subgroup of patients with dyslipidemia and Acute Cerebrovascular Event, a statistically significant predominance of the number of AG genotype carriers (р=0.008) and a decrease in the number of AA genotype carriers (р=0.002; OR 2.11, 95% CI 1.323.38) compared to control. With respect to the GG genotype, no statistically significant differences were obtained as in the subgroup of patients with brachiocephalic artery atherosclerosis (р=0.05). The rare G allele was statistically significantly more common among patients with dyslipidemia and Acute Cerebrovascular Event than among the control group (р=0.001; OR 2.01, 95% CI 1.353.16). In a subset of patients with impairment in the hemostasis system who underwent Acute Cerebrovascular Event, similar results were obtained. So, among patients with hypercoagulation, the frequency of carrying the AA genotype was 63.8%, the frequency of the AG genotype was 33.0%, and the frequency of the GG genotype was 2.3%. In a subgroup of patients with impaired hemostasis and Acute Cerebrovascular Event, a statistically significant predominance of the number of AH genotype carriers (р=0.001) and a decrease in the number of AA genotype carriers (р=0.000; OR 2.74, 95% CI 1.594.72) compared to control. No statistically significant differences were obtained with respect to the GG genotype (р=0.09). The wearing of the rare G allele was statistically significantly more common among patients with hypercoagulation and Acute Cerebrovascular Event than among the control group (р=0.000; OR 2.50, 95% CI 1.544.05). Conclusion. The results of our study suggest the need for further investigation of this polymorphic variant in order to study the possible mechanisms of its influence on the development of CVD and cerebrovascular pathology. We may suggest that the wearing of the AG genotype and the G allele rs662799 (AG) increase the risk of Acute Cerebrovascular Event in patients regardless of previous CVD and risk factors, including those with AH, supra-ventricular tachyarrhythmias, brachiocephalic artery atherosclerosis, impaired lipid metabolism and hemostasis systems.

Abstract: Aim. To study a contribution of polymorphism A-8202G (rs11697325) of a gene of matrix metalloproteinase-9 (MMP-9) in development of arterial hypertension (AH) in patients with the rheumatoid arthritis (RA). Materail and methods. 143 patients with RA were examined, among which a group of patients with RA without AH (n=50) and a group of patients with RA in association with AH (n=93) were identified. Healthy volunteers (n=151) were also divided into 2 groups comparable in age, sex and number with the main groups (control group 1 n=54, control group 2 n=97). The work used a range of clinical, laboratory, instrumental methods. A molecular genetic study was also performed. Blood samples were taken from all study participants. DNA isolation was carried out by the standard phenol-chloroform method. Genotyping for the MMP-9 gene was performed by PCR-RFLP analysis (polymerase chain reaction restriction fragment length polymorphism). PCR was carried out with a set of primers to the corresponding regions of the genome. PCR products were analyzed by electrophoresis in 4% polyacrylamide gel followed by staining with ethidium bromide. Results. In the course of a molecular genetic study, a statistically significant predominance of the homozygous AA genotype and the A allele of the MMP-9 (rs11697325) gene polymorphism was observed in the group of patients with RA, both separately and in association with AH, in comparison with the data of control groups. The risk of developing RA estimated by the odds ratio (OR) in carriers of the AA genotype of the MMP-9 gene is 1.8 times higher (95% confidence interval CI 1.1362.950; p=0.02) than in carriers of the GG and GA genotypes; in carriers of the A allele, the risk of developing RA is 1.6 times higher compared to the G allele (95% CI 1.1192.578; p=0.01). The OR risk of developing RA in association with hypertension in carriers of the AA genotype of the MMP-9 gene is 2.8 times higher (95% CI 1.2836.54; p=0.04) compared to GA and GG genotypes, 2.1 times higher in carriers of the A allele (95% CI 1.1134.127; p=0.02) compared to the G allele. Conclusion. Thus, the results of the study indicate that the homozygous AA genotype and the A allele of the MMP-9 (rs11697325) gene polymorphism are the predictors of the development of RA both as a separate nosological unit and in association with AH.

Abstract: The paper describes the investigation of matrix metalloproteinase type 3 (MMP-3) -1171 5A/6A gene polymorphic alleles variants (rs35068180) in patients with dilated cardiomyopathy. A allele and 6А6А genotype of MMP-3 -1171 5A/6A gene (rs35068180) were determined as new genetic predictors of dilated cardiomyopathy development. Aim. To study the association of polymorphism -1171 5A/ of the MMP-3 gene with dilated cardiomyopathy of various origins. Material and methods. The main study group comprised 221 patients with dilated cardiomyopathy (DCM) of different origin. Their average age was 55.309.69 years. Among them there were 111 persons with DCM of ischemic origin, including 99 (89.2%) men and 12 (10.8%) women. The average age of the subjects with DCM was 51.739.74 years, the age of the male subgroup was 51.008.96 years, and the age of the female subgroup was 57.753.71 years. A total of 110 patients with idiopathic cardiomyopathy were included in the study. Among 221 patients, 110 persons did not demonstrated idiopathic dilated cardiomyopathy as the cause of myocardium dilation. This group comprised 100 (91.5%) male patients and 10 (8.5%) female patients. The control group of subjects (221 persons) was represented by healthy people without diseases of the cardiovascular system. The average age of control subjects was 53.64.8 years. We examined all patients in the main group using routine laboratory and instrumental methods, as well as coronary angiography. If myocarditis was suspected, we did an MRI of the heart. Genotyping of polymorphism -1171 5A/6A (rs35068180) of the MMP-3 gene was performed using PCR. Results. Among patients of the main group with dilated myocardial remodeling of various Genesis, the allele was documented in 65.8% of cases against 59.3% among the control group, p=0.044. The homozygous genotype of the MMP-3 gene in patients of the main group was verified in 42.1% of patients against 32.6% of cases in relatively healthy individuals (p=0.099). Conclusion. We have proved the predominance of 6A allele and 6А6А genotype of the MMP-3 gene in the group of patients with DCM. It seems that it is homozygous 6A allele that causes a decrease in the activity of the transcription process and change in the level of stromelysin in arterial walls. This contributes to the activation of type 1 procollagenase, extracellular matrix deposition and cardiac muscle remodeling.

Abstract: Atrial fibrillation is one of the most common heart rhythm disorders. The most prominent risk factor for atrial fibrillation is advanced age. Population ageing contributes to an increase in both the prevalence of this pathology and socio-economic burden of the disease for society in general and the patient in particular. Adequate therapy and prevention of atrial fibrillation requires the search for novel prognostic risk markers for disease development, progression, and patients response to therapy. One of these markers is the length of telomeres structures at the ends of chromosomes that protect them from degradation during cell division. The article provides an overview of world studies, both confirming and disproving the role of leukocyte telomere length in atrial fibrillation development.