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Understanding the molecular mechanisms of atherosclerotic vascular lesions formation is necessary both for assessing the risks of cardiovascular diseases and for finding approaches to their therapy. The task remains relevant, despite the large number of studies carried out, because there are differences in the factors of genetic predisposition to atherosclerosis and its complications between different ethno-territorial groups. The aim of this study was to search for genetic variants of pattern recognition receptors associated with lipid metabolism disorders that can lead to the development of coronary atherosclerosis (CA).Material and methods. Analysis of exons and adjacent splicing sites of pattern recognition receptors genes in patients with CA (30 men), and then genotyping of a population sample from Novosibirsk (n = 1441) by real-time PCR for selected rs113706342 of the TLR1 gene and analysis of associations of its carriage with lipid metabolism were performed.Results and discussion. The frequency of the minor allele rs113706342 C of the TLR1 gene in the sample of residents of Novosibirsk was 0.0114 ± 0.0062, the carriage of this variant was associated with an increased level of low-density lipoprotein cholesterol in both women and men (p = 0.009 and p = 0.019, respectively). Women carriers of the minor allele C for rs113706342 also had a statistically significant increase in total serum cholesterol (p = 0.013) compared with TT homozygotes. To test the role of this variant in the development of CA, genotyping of an extended sample of patients is required. In one of the patients with CA, a previously undescribed single nucleotide variant chr16:3614637 G/C was found, leading to the Leu101Val substitution in the NLRC3 gene; segregation analysis is required to assess its functional significance.Conclusions. The association of rs113706342 C of the TLR1 gene with lipid metabolism disorders in the Russian population is shown.

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.

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

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

Cardiovascular diseases, in particular myocardial infarction (MI), are one of the most common causes of death in the world. Today, a significant problem for assessing of MI and post-infarction complications risks is the insufficient sensitivity and prognostic values of modern methods and markers. Therefore, the identification of new markers with high specificity and sensitivity is an important task. Recently, much attention has been paid to the study of extracellular RNAs, which are relatively stable in biological fluids. In this article, we overviewed some miRNAs, which are considered as potential markers for the diagnosis of MI and prediction of its adverse effects.

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

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

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

Aim. Assessment of the associations of mononucleotide polymorphisms (MNP) of genes: KCNN2 (rs13184658, rs10076582, rs338625) and NOS1AP (rs12567209, rs348624, rs3751284, rs 12143842), with sudden cardiac death (SCD), and evaluation of the clutch units.Material and methods. The study designed as a case-control. Group of males, died SCD (n=278) was formed according with the European Cardiology Society criteria. The controls (n=274), matched by age and gender, was collected from DNA of international research projects MONICA and HAPIEE. Genomic sequencing was done with real time PCR. For inequation assessment of the clutch groups within the MNP pairs, the D’ coefficient was in use. Comparison of the groups by the rates of genotypes and alleles was done with a contingency tables and Chi-square by Pearson. Relative SCD risk was calculated as an odds ratio with Fischer criteria and Chi-square. The differences were noted as significant with p

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

Abstract Objective Earlier, GLIS3 gene polymorphisms have been shown to be associated with the development of maturity onset diabetes of the young (MODY). We screened GLIS3 gene sequences among patients with MODY to identify probably pathogenic variants by whole-exome sequencing. We estimated frequency of rare single-nucleotide variants in the coding region of GLIS3 in a Caucasian population and among individuals with carbohydrate metabolism disorders in Russia. Results We identified 15 single-nucleotide variants in GLIS3. Three rare variants (minor allele frequency

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

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

Background and aims: mutations in LDLR, APOB, PCSK9 genes determine the development of autosomal dominant forms of familial hypercholesterolemia. The PCSK9 gene encodes an enzyme involved in the metabolism of low density lipoprotein (LDL) by post-transcriptional regulation of the LDL receptors. Purpose: to perform analysis of PCSK9 rs562556, rs11591147 in Russian population and the population sub-samples of persons with hyper- and hypocholesterolemia; to investigate the PCSK9 protein association with rs562556, rs11591147 the PCSK9 gene at the population level. Materials and methods: genotyping rs562556 in the PCSK9 was carried out in a population and in the subgroup with hypercholesterolemia; genotyping rs11591147 was carried out in a population and in the subgroups with normal and low level of total cholesterol. Subgroups were included in the analyses in the HAPIEE project framework (9360 participants, 45-69 years old, 50% men). Blood lipid levels were determined using standard enzymatic assays. Genotyping of the PCSK9 rs11591147 was performed using PCR-RFLP and then confirmed by direct sequencing. Genotyping of the PCSK9 rs562556 was performed by RT-PCR using sets of "Syntol" (Russia). Results:Analysis of rs562556 association with lipid profile and PCSK9 protein blood levels showed these polymorphisms do not significantly contribute to forming hypercholesterolemia in Caucasian populations of Western Siberia."Loss of function" mutation R46L (PCSK9 rs11591147) association with total cholesterol levels in the group with normal and low levels of total cholesterol was revealed. Conclusion: The PCSK9 rs562556, rs11591147 alleles and genotypes frequency in the population and in the population subgroups with hyper- and hypocholesterolemia were determinedfor the first time in Russia. The Caucasian population of West Siberia does not significantly differ from populations of Europe by alleles and genotypes frequencies.A statistically significant association of the rare T allele of rs11591147 with low total cholesterol was determined.

Familial hypercholesterolemia (FH) is one of the most common congenital metabolic disorders. Cascade genetic screening used for diagnostic of patients with FH. Aim of study is to explore the awareness of FH patients of the problem of familial hypercholesterolemia and conduct a pilot study of patients with FH using the principle of a cascade genetic screening. The study was performed in patients with a clinical diagnosis of “definite” FH. The study was approved ethics committee. Target was selected for high-throughput sequencing (GS Junior, Roche). Participation in the survey was voluntary and anonymous. An analysis of the responses to the questions provided data on the lack of awareness of patients with the FH about the problem. Certain mutations in this study and LDLR gene polymorphisms confirmed genetic heterogeneity of the spectrum of structural modifications of LDL receptor gene in patients with FH.

Aim. The study of mononucleotide polymorphisms associations rs20455 gene KIF6, rs7439293 gene PALLD, rs2298566 gene SNX19, rs3900940 gene MYH15, rs1010 gene VAMP8, included into the Riskometer of ischemic heart disease of the Celera Corporation (USA), in sudden cardiac death.Material and methods. To the study the group of persons included, died from sudden cardiac death, according to the WHO criteria (n=352, mean age — 53,3±8,9 y.), control group from matched by age and gender from DNA bank of HAPIEE, MONICA studies (n=381, mean age — 53,1±8,3 y.), adolescents group (n=296, mean age — 15,6±0,9 y.). DNA extracted via the phenol-chloroform extraction from myocardium of the dyed due to sudden cardiac death, and from venous blood of controls. Genotyping performed with Real-time PCR method using the Taq-Mancatheters technology (Applied Biosystems).Results. The prevalence of alleles rs7439293 gene PALLD, rs2298566 gene SNX19, rs3900940 gene MYH15 did not statistically significantly differ among the groups. In those died suddenly older than 50 years, there was significant decrease of carriers of GG polymorphism rs20455 gene KIF6 (9,0%) comparing to the controls (17,8%) (р=0,009, OR=0,456, 95% CI 0,256-0,810). In men older 50, died suddenly, there was significant decrease of the carriers of genotype СС (8,0%) (р=0,002, OR=0,328, 95% CI 0,159-0,678) and increase of СТ genotype (49,6%) (р=0,025, OR=1,729, 95% CI 1,084-2,758) polymorphism rs1010 gene VAMP8 comparing to the controls (21,0%, 36,3%, respectively). Conclusion. Polymorphisms rs20455 gene KIF6 and rs1010 gene VAMP8 are associated with sudden cardiac death.

Study objectives: examine the frequency of genotypes and alleles of I/D polymorphism of gene ADRA2B of native people living in Mountain Shoria (the Shors), as well as their association with risk factors for cardiovascular diseases.Material and methods. Overall 221 native people of Shoria were examined. The average age is51.07 ± 1.46 among males, 52.93 ± 0.96 among females (p = 0.286). Anthropometric characteristics, lipid levels of blood and I/D polymorphism of ADRA2B were studied.Results. DD genotype of the gene ADRA2B in the native population of the Shor people is associated with adiposis and high index of "waist/hip", hypertriglyceridemia. The average values of Quetelet index is higher in carriers of this genotype compared with carriers of genotype ID. Average waist indications in homozygous insertions were lower than those in homozygous deletions and heterozygotes. Patients with genotype DD have higher average levels of triglycerides, atherogenic index, cholesterol, very low density lipoproteins.Conclusion. DD allele ADRA2B genotype is responsible for adiposis and high levels of TG among native population of Shoria.

Aim: replication of association the SNPs with myocardial infarction (identified in recent GWAS) as markers of risk for myocardial infarction (MI) in a Siberian population. Methods: Group of MI patients and control group (ratio 1:2) were formed on the sample of population 45–69 years old resident of Novosibirsk (9400 people), which was collected in international project HAPIEE (Health, Alcohol and Psychosocial factors In Eastern Europe). A total of 94 patients (60 men and 34 women with myocardial infarction after study HAPIEE). Control group: individuals without MI (420), matched for age and sex. Genomic DNA was extracted from venous blood by phenol-chloroform extraction. Polymorphism of genes tested by real-time PCR according to the protocol producer firms (probes TaqMan, Applied Biosystems, USA) on the instrument ABI 7900HT. The study was taken following SNPs: rs499818, rs619203, rs10757278 and rs1333049 (hr. 9), rs1376251, rs2549513, rs4804611, rs17465637. Results: Rs10757278 and rs1333049 for the show were the association with MI OR = 1.78 (95 % CI 1.07–2.97 p = 0.03 GGvsSS + CG), and SS OR = 1.78 (95 % CI 1.07–3.02 p = 0.03 SSvsGS + GG ), respectively. Just for rs1376251 (TAS2R50) shows protective role in relation to them TT OR = 0.22 (95 % CI 0.05–0.91 p = 0.02 TTvsCC + CT), for the remaining SNPs statistically valid data has been received. Conclusion: Thus in this study were confirmed by the association rs1333049 (Mts. 9), rs10757278 (Mts. 9) with myocardial infarction and shows the new relationship with Russia for myocardial infarction for rs1376251 (TAS2R50).

Aim. To evaluate the relationship of 8 mononucleotide polymorphisms (MNP) with negative longterm prognosis of the acute coronary syndrome.Material and methods. Totally 280 patients with acute coronary syndrome included (ACS), who during 1 year follow up were underwent the solid endpoints evaluation (cardiovascular death, hospitalization for recurrent ischemic event and repeated revascularization).Results. In the analysis of rs4804611 in group with negative outcomes there is significantly more prevalent genotype GG (9,1% vs. 1,8%), chances relation 5,57 (95% CI 1,35-22,96); credibility of the differences kept in men (p=0,021). In the analysis rs2549513 in the group with positive prognosis the AA genotype was more prevalent (70,6% vs. 53%), hazard ratio 0,47 (95% CI 0,26-0,85), and in the group with negative prognosis genotype AC, chances relation 2,32 (95% CI 1,28-4,20; р=0,007).While separated by gender credible differences were shown only in men (p=0,008).Conclusion. Evaluation of genetic markers rs4804611 and rs2549513 can significantly increase prognostic value in riskometry of ACS outcomes.

Aim. To search and study the association of some candidate genes polymorphysms of various cardiovascular diseases and sudden cardiac death in men.Material and methods. The sudden cardiac death group (SCD) is collected by the WHO criteria with suddenly died men underwent court-medicine expertise (n=274). Control group was matched by the age and gender from the DNA bank of HAPIEE and MONICA trials. Genotyping of groups was done according to polymorhysms SCN5A, rs187238 gene IL-18, rs1799864 gene CCR2, rs3864180 gene GPC5, rs1799983 gene eNOS, rs2228314 gene SREBF-2, rs1800588 gene HL, rs10757278, rs1333049 with methods of PDRF and realtime PCR.Results. No significant differences found between the SCD group and control group by the prevalence of genotypes SCN5A, rs187238 gene IL-18, rs3864180 gene GPC5, rs1799983 gene eNOS, rs1800588 gene HL.In SCD group the decrease of homozygotes by CC polymorphism rs2228314 found in gene SREBF-2 and the decrease of heterozygotes GC comparing to control group (HR=4,074, 95% CI 1,843-9,002, р=0,0002; HR=0,442, 95% CI 0,302-0,647, р=0,0001, reap.). In SCD group carriers of GG genotype polymorphism rs10757278 and CC poly morphism rs1333049 are significantly more prevalent than in control group (HR=1,814, 95% CI 1,159-2,839, р=0,011; HR=1,744, 95% CI 1,104-2,754, р=0,019, resp.). The part of GA carriers of polymorphism rs1799864 gene CCR2 is more prevalent in SCD group comparing to control (HR=1,558, 95% CI 1,051-2,308, р=0,029).Conclusion. Polymorphisms rs10757278, rs1333049, rs2228314 gene SREBF-2, rs1799864 gene CCR2 are associated with sudden cardiac death in men.

Aim. To check whether the mononucleotide polymorphisms (MNP), identified in recent studies do match a risk marker criteria for arterial hypertension (AH) in Siberian population.Material and methods. The group of subjects with AH and control group (relation 2:1) were formed from the population selection of 45-69 years old citizens of Novosibirsk (9400 subjects), which had been collected during the work in HAPIEE project. Totally 514 subjects included, of those controls – 168 (127 men and 41 women) with BP not higher than “normal” by the data of 2 and more examinations during the last years, with interval not more than 6 months. Group with AH consists of 346 subjects (206 men and 140 women) with the diagnosis of AH. Genomic DNA was extracted from venous blood by the method of phenol-chloroform extraction. Gene polymorphism was tested by PCR in real time according to the protocol of equipment manufacturer (zonds TagMan, Applied Biosystems, USA) on the device ABI 7900HT. These MNP were included into the study: rs699 gene AGT, rs5068 gene NPPB, rs17367504 gene MTHFR, rs2681492 gene ATP2B1, rs4343 gene АСЕ, rs1801253 gene ADRB1, rs11240692 gene REN, rs2846679 gene KCNJ1, rs239345 gene SCNN1B, rs1799983 gene NOS3.Results. The risk relation to develop AH in men – carriers of GG rs699 gene AGT was1,95 (95% CI 1,08-3,53; p=0,003) comparing to the carriers of two other genotypes. Carriage of AA genotype rs699, opposite, is probably protective factor for AH development in men (HR 0,47; 95% CI 0,27-0,81; p=0,007).Conclusion. For two from ten MNP studied the association with AH was confirmed in men: rs699 gene AGT and rs5068 gene NPPB.

Study objective. Investigate the association of polymorphisms E2/E3/E4 gene APOE, rs1800588 gene HL, rs2228314 gene SREBP2, rs2516839 gene USF1 with sudden cardiac death in the Russian population. Materials and methods. A group of sudden cardiac death (n = 379), the control group, matched by sex and age (n = 352). Results and discussion. The frequencies of genotypes E2/E3/E4 gene APOE, rs1800588 gene HL, rs2516839 gene USF1 was not found statistically significant differences between the groups. The frequencies of genotypes rs2228314 gene SREBP2 found statistically significant differences between the group of sudden cardiac death and the control group. GC genotype is conditionally protective against the development of sudden cardiac death (OR = 0.4, 95 % CI 0.3–0.6, p = 0.0). CC genotype is associated with an increased risk of sudden cardiac death in men (OR = 4.1, 95 %CI 1.8–9.0, p = 0.0). Conclusion. rs2228314 gene SREBP2 is associated with sudden cardiac death in the Russian population.

Aim. To investigate the association between single-nucleotide polymorphisms (SNPs) rs10757278 and rs1333049 of the 9p21.3 locus and family history of coronary heart disease (CHD) in myocardial infarction (MI) patients. Material and methods. The MI group (n=243) and the control group (n=280) were comparable by such parameters as age, gender, arterial hypertension, diabetes mellitus, hypercholesterolemia, overweight and obesity, abdominal obesity, and smoking history. However, the groups were significantly different in terms of family history of CHD (p=0,004). Genome DNA was extracted from venous blood using the phenol-chloroform extraction method. The SNPs rs10757278 (9p21.3) and rs1333049 (9Sр21.3) were tested using real-time polymerase chain reaction (PCR) and the AB 7900HT device, according to the producer’s protocol (TaqMan probes, Applied Biosystems, USA). Results. A statistically significant association between MI and the CC rs1333049 genotype or the GG rs10757278 genotype was observed in the whole study sample and separately in men and women. The MI odds ratio (OR) for carriers of the CC rs1333049 genotype was 2,02 (95% confidence interval, CI, 1,32–3,08) in the whole sample, 1,91 (1,11–2,95) in men, and 2,91 (1,22–6,91) in women. For carriers of the GG rs10757278 genotype, respective OR values were 1,98 (1,30– 3,02), 1,77 (1,08–2,87), and 2,94 (1,26–6,87). Among participants without CHD in family history, OR for the CC rs1333049 genotype (1,92, 95% CI 1,16–3,16) and the GG rs10757278 genotype (1,82, 95% CI 1,10–3,00) were comparable for those among MI patients with CHD in family history (respective OR 2,19 (1,28–3,75) and 2,23 (1,31–3,81)). Conclusion. For the first time in Russia, the association between MI-related polymorphisms of the 9p21.3 chromosome and family history of CHD was analysed. Two SNPs (rs1333049 and rs10757278) of the 9p21.3 locus predicted MI risk independently from either conventional risk factors or CHD in family history.

The article deals with issues of necessity of training and development of working staff for construction industry of Russian Federation for creation of competitive construction industry, meeting the high quality and efficiency standards, working in basis of modern financial and economic, technical and management mechanisms. One of the ways to solve this task of innovative development is modernization of architectural and building design, in particular implementation of BIM technology enabling making efficient decisions at all stages of building and structures life cycle – from investment concept till operation and even demolition. In relation to this the industry demands highly qualified workers and engineers (bachelor students) being able not only to get new knowledge but to use them for solving practical tasks of modern construction industry and market.The article present a concept of designing educational programme for training students with major 08.03.01 «Construction» (bachelor degree) focusing on systematized knowledge, skills and tools for training, in particular, through interconnection and continuity during course and diploma papers based on BIM technology.

The paper examines an issue of ensuring reliable power supply to construction facilities, proposes ways to reduce losses in distribution networks and improve power supply reliability.The primary focus is on increasing the transmission capability of power distribution networks and improving power supply reliability and safety of single-phase electricity consumers.Engineering and technical proposal belongs to the field of electrical engineering and in particular concerns power supply to single-phase consumers from three-phase networks, including construction industry consumers, and can be used in three-phase three-, four- and five-wives alternating current power distribution networks.