Aim. To analyze possible association of the risk of adverse outcomes development in patients post acute coronary episode (ACS), with the polymorphism of gene TNF.

Material and methods. To the study, patients included, that were under observation in 2 registry studies ORACLE I and II (Exacerbation of coronary heart disease: logic-probability ways of course prediction and treatment optimization). In overall, 2012 ACS patients assessed. Mean age 64,7±12,69 y.o. There were 1205 males (59,8%) and 807 females (40,2%). 741 patients (36,8%) included with ST elevation ACS, 1271 (63,2%) — with non-ST elevation ACS. Follow-up started at the 10th day from clinical stabilization. Clinical outcomes were gathered based on phone calls with the patients and their relatives, as during the outpatient office visits. Assessment of polymorphisms of gene TNF done with PCR.

Results. In the assessed group, the frequency of alleles and gene TNF genotypes were measured: 18 patients carried genotype АА (0,9%), 561 patients — AG (279%), 1433 — GG (71,2%). In those with the allele А gene TNF, more commonly the episodes of SCD were noted (9,8% comparing to 6,6% of GG carriers, p<0,001); rate of non-cardiac death did not differ significantly (3,5% and 3,1%, respectively). There were no significant differences in the rate of fatal and non-fatal strokes, number of non-complicated cases of peripheral atherosclerosis. In the group of patients with allele A, there were more common the repeated ACS episodes (21,4% vs 12,8% in GG carriers, p<0,001). The rate of repeated after discharge interventions did not differ significantly. Independent factors for any adverse outcome (death, ACS, stroke, complicated atherosclerosis, repeated coronary interventions) were myocardial infarction (OR 1,235 (1,041-1,464)) and heart failure (OR 1,22 (1,02-1,44)) in anamnesis, decreased GFR (OR 1,04 (0,87-1,43)) and carriage of АА and AG gene TNF (OR 1,35 (1,14-1,60)).

Conclusion. Carriage of the rare A allele of polymorphic marker G(-308)A gene TNF is associated with more common development of adverse outcomes in patients after exacerbation of CHD.

Aim. To study the associations of allelic variants of the CYP2C19 gene with atherosclerotic lesions of the coronary arteries in patients with acute coronary syndrome (ACS) in the North of Siberia (Surgut) and in large cities of the Siberian Federal Okrug (SFO).

Material and methods. During the study 296 patients with ACS were examined at admission to cardiology hospitals in large cities of the North (Surgut, 114 patients) and SFO (Irkutsk and Kemerovo, 182 patients). All patients underwent coronary angiography and genetic research (identification of CYP2C19*2, CYP2C19*3 and CYP2C19*17 alleles).

Results. In patients with ACS living in the North of Russia allelic variant CYP2C19*17 (*17/*17) is positively associated with the severity of lesion of left coronary artery (LCA) (χ²=9,81; p=0,002), as well as with at least 50% stenosis, more than 70% lesion of the proximal or middle part of the three main arteries, or more than 50% lesion of LCA trunk (χ² =6,52; p=0,011), and previous myocardial infarction (χ²=8,15; p=0,004). Among patients with ACS living in cities of the Siberian Federal Okrug, the allelic variant CYP2C19*17 (*17/*17) is directly associated with diabetes mellitus (χ²=5,48; p=0,019) and less than 45% left ventricular ejection fraction (χ²=4,20; p=0,040). Regression analysis showed that in patients with ACS living in the northern region of Russia, only the allelic variant CYP2C19*17 (*17/*17) correlated with at least 50% stenosis of LCA trunk (Exp (B): 11,623, 95% CI: 1,893; 71,342; p=0,008). It did not correlate with the male sex, age, smoking and diabetes (p>0,05).

Conclusion. The results show the presence of direct associations of CYP2C19*17 alleles with prognostically unfavorable coronary atherosclerosis in ACS patients living in the North of Siberia.

Aim. To study the occurrence of allelic variants of folate cycle enzymes’ genes, which are unfavorable with respect to the risk of thrombophilia, to analyze the serum level of homocysteine, and to assess their impact on the development of acute coronary syndrome (ACS) in non-obstructive coronary atherosclerosis (NOCA).

Material and methods. The material for the study was the results of a non- randomized, open, controlled conduct research, NCT02655718' conducted in 2015-2016 in the emergency cardiology department. The sampling included patients older than 18 years with ACS and NOCA, confirmed by invasive coronary angiography (ICAG). Patients who had previously undergone coronary artery revascularization were excluded from the study. We analyzed four polymorphic genotypes of folate cycle enzyme genes of included patients: methylene-tetra- hydro-folate-reductase MTHFR (677 C>T, 1298 A>C), methionine synthetase MTR (2756 A>G), methionine synthetase reductase MTRR (66 A>G). Determination of genotypes was performed using the methods of polymerase chain reaction and the use of a set of reagents produced by OOO “DNK-Tekhnologiya”. The level of homocysteine was determined by the enzyme immunoenzyme technique using Axis (UK) set of instruments for diagnosis and standards methods.

Results. In 2015-2016 913 patients with ACS were hospitalized in emergency cardiology department; 44 (4.8%) were patients with NOKA. The mean age was 54±11 years (68% men). Mean level of homocysteine in the examined patients was 12,2 (10,8; 13,6) umol/l, in men — 12,4 umol/l (11,5; 13,6), in women — 11,3 umol/l (9,5; 13,2). Hyperhomocisteinemia (HHC) was registered in 8 (18%) individuals. The median level of homocysteine in patients with HHC was 22,8 (17,2; 25). An increase in the ultra-sensitive C-reactive protein and diagnosing of acute myocardial infarction (AMI) were more common in patients with HHC. The level of homocysteine did not differ in patients with various degrees of coronary artery stenosis; it was associated with age, hereditary background, smoking and the carriage of an unfavorable homozygous polymorphic variant of the TT genotype MTHFR gene (677 C>T). The carriage of the unfavorable TT genotype MTHFR (677 C>T) was statistically significantly more common in patients with AMI. The carriage of unfavorable homo- and heterozygous genotypes of the MTHFR gene (677 C>T) in the group without HHC was also detected. The ancestral allele C of the rs1801133 gene was statistically significantly more common in intact coronary arteries.

Conclusion. In this study 96,6% of patients with ACS and NOCA were carriers of unfavorable polymorphic variants of folate metabolism genes. The carriage frequency of unfavorable T allele of rs1801133 gene is statistically significantly more common in patients with AMI. The presence of this genotype is associated with the development of HHC, which is equivalent of literature data. However, the presence of the allelic variant of TT MTHFR (677 C>T) did not always lead to the development of HHC. An increase in plasma homocysteine levels is directly proportional to age, hereditary background, smoking, and carriage of the TT rs1801133 genotype. It is also associated with an increased risk of AMI, which confirms previous studies.

Aim. To study the relationship of rs1800470 polymorphic variants of the transforming growth factor p1 (TGF-β1) gene with the severity of coronary arteries (CA) atherosclerosis.

Material and methods. The study included 256 patients with myocardial infarction (MI) (216 males and 40 females) of a Caucasoid race aged <65 years (52,1 ±8,4). Phenol-chloroform extraction was used for separating DNA from venous blood. The rs1800470 polymorphism of TGF-β1gene was tested using real-time polymerase chain reaction (PCR) (TaqMan probes, AB 7900HT). The assessment of coronary bed lesion severity was made according to the protocol of standard polyprojection coronary angiography with using of Gensini scores.

Results. For the first time in the Siberian population, the relationship of the A rs1800470 allele of the TGF-β1gene and severity of coronary atherosclerosis has been proved in men. The carriers of the rs1800470 allele A of the TGF-β1 gene had a odds ratio (OR) of the multivessel CA lesion (OR =2,84 (95% CI 1,37-5,87), p=0,004) and proximal type coronary atherosclerosis (OR =2,66 (95% CI 1,29-5,47), p=0,007). In general, the Gensini score was significantly higher in carriers of the risk A rs1800470 allele of the TGF-β1 gene: AA genotype — 57,33±41,89; AG genotype — 52,86±40,74; GG genotype — 43±28,83 (p>0,05), however, the differences were statistically significant in the upper quartile (p=0,028). OR of severe damage to CA (Gensini score >80 points) in carriers of the A rs1800470 allele of the TGF-β1 gene was 3,64 (95% CI 1,06-12,49). In women, no statistically significant correlation of the rs1800470 genotype of the TGF-β1 gene with the severity of CA lesions was identified.

Conclusion. A rs1800470 allele of TGF-β1 gene is associated with the severity of coronary atherosclerosis in men.

Genetic background of hypertension (AT) and blood pressure (BP) regulation is extensively investigated in genome-wide association studies (GWAS). The findings from recent GWAS require replication in independent samples.

Aim. To investigate the association between BP and AT in Russian population and several single nucleotide polymorphisms identified in GWAS.

Material and methods. In the frame of “case-control” design we recruited subjects with AT diagnosed at age below 50 according to the criteria of BP >140/90 mm Hg and/or receiving antihypertensive therapy, and subjects with normotension according to 2 examinations from population sampling, Novosibirsk, totally included 514, men/women aged 45-69 years). From published GWAS we selected 24 genetic markers related to hypertension, 8 markers were included for present analysis (rs 13082711, rs1173771, rs13107325, rs3918226, rs1799945, rs805303, rs1458038, rs932764). Standard epidemiological methods were used (BP measurement, anthropometry, medical history of AT and treatment, risk factors of AT, socio-demographic parameters). Single nucleotide polymorphisms (SNPs) were tested using real time PCR.

Results. In studied sample we replicated the association between rs3918226 (promoter region of gene of endothelial NO synthase; eNOS) and systolic BP (T-allele carriers had 9 mm Hg higher systolic BP than CC carriers in men, p=0,049 independent of age). New association was found between rs 932764 (gene of phospholipase-c-epsilon-1 isoform, PLCE1) and AT (heterozygotes genotype AG was protective in men, p=0,017 independent of age and body mass). The association between rs13107325 (gene of soluble carrier family 39/zinc transporter/member 8, SLC39A8) and systolic BP was confirmed (in men, С-allele carriers had higher systolic BP values then TT carriers, p=0,044, multivariable adjusted).

Conclusion. In analysis of relationship between phenotypes of BP and AT and 8 genetic markers of AT in Russian population sample we replicated two known associations, revealed new association and identified new data on modulating effect of sex and body mass. These replications in newly studied Siberian population, different from early studied populations by risk factors profile, climate, geographic and other parameters, support the involvement of identified or close loci in potential mechanisms of AT susceptibility.

Aim. To study the involvement of polymorphic loci rs1799750 MMR1, rs3025058 MMR3, rs 11568818 MMR7, rs1320632 MMR8 and rs11225395 MMR8 in the development of arterial hypertension (AH) in women of the Central Chernozemny Region of Russia.

Material and methods. During the study 584 women were examined: 375 patients with AH and 209 control subjects. Analysis of metalloproteinases’ polymorphic loci was performed using real-time PCR (TagMan probes). Statistical processing of the results was performed using the STATISTICA for Windows 10.0. The regulatory potential of polymorphic loci was analyzed using the HaploReg software (v4.1). Assessment of the effects of single nucleotide polymorphisms on gene expression (cis-eQTL) was performed according to the Genotype-Tissue Expression (GTEx) project.

Results. We established that the polymorphic allele G (OR=1,49, 95% CI=1,16-1,92, p=0,002) and the GG genotype (OR=1,64, 95% CI=1,12-2,40, p=0,010) in the rs11568818 locus of MMP7 gene is associated with a high risk of AH in women. Polymorphic marker rs11568818 MMP7 has significant epigenetic effects: located in the region of histones, labeling promoters and enhancers, in the region of binding sites with transcription factors Foxa known1, PLZF, Pou5f1 known2 and GR known4, in binding niche of regulatory proteins TBP, c-FOS, c-Jun. It was found that the polymorphic variant G rs1 1568818 of MMP7 is associated with a reduced level of expression of the MMP7 gene.

Conclusion. The polymorphic locus rs11568818 of the MMP7 gene is involved in the development of AH in women of the Central Chernozemny Region of Russia.

Aim. To identify the factors of long-term adverse prognosis of patients with acute coronary syndrome as a result of five-year follow-up.

Material and methods. The study included 280 patients with ACS hospitalized in the 1st cardiology Department of the Novosibirsk municipal CLINICAL hospital № 1 in 2010-2011. The study cohort included 145 patients with ACS (107 men and 38 women), 135 patients with ACS (93 men and 43 women). The average age of men was 56,3±5,2, women 52,1±5,3 years. The criteria of the European society of cardiology (2015, 2017) were used for the diagnosis of ACS. For five years, all patients included in the study were contacted through communication and annual medical examinations, to which patients were invited to the clinic. The examinations included the following clinical and instrumental examinations: clinical examination, electrocardiography, Holter monitoring of electrocardiogram, echocardiography, lipid profile, inflammatory cytokines and molecular genetic parameters. In the study, a mathematical model for predicting five-year outcomes Oxpt and Oxbt.

Results. Five-year observation allowed using the constructed mathematical model to determine not only the place of each factor in the cardiovascular prognosis, but also to assess how the role of these prognostic markers changes over time.

Conclusion. The use of a mathematical model for predicting long-term adverse outcomes of ACS allows to assess the value of specific risk factors and predictors, respectively, makes a significant contribution to the optimization of secondary prevention and personalized approach to treatment. At the same time, the influence of the identified predictors weakens in proportion to the increase in the number of years from a vascular accident. Thus, the identified risk factors have the maximum impact in the first year after ACS, in subsequent years, the role of these factors is reduced, which is probably due not only to the importance of the factors themselves, but also to the addition of other risk factors to the overall picture of the disease of patients. Nevertheless, the use of this model is necessary to solve the problem of reducing cardiovascular risk.

Aim. The aim of the study was to assess the association of genetic polymorphisms of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) with atrial fibrillation development in elderly patients with coronary artery disease (CAD), undergoing coronary artery bypass graft (CABG) surgery.

Material and methods. Studied were 80 patients who underwent CABG in 2015-2016 years. In all the patients routine laboratory and instrumental tests were performed. Patients also underwent genetic polymorphisms of ММР-9 А8202G and TIMP-1 C536T estimation with polymerase chain reaction. According to occurrence of postoperative atrial fibrillation (POAF) all the patients were divided into two groups: 1 group comprised 56 patients without POAF (81,8% males, mean age 65,9±4,0 years), 2 group — 24 patients with first detected episode of AF after CABG (875% males, mean age 67,7±5,4).

Results. According to results of multivariate regression analysis the odds ratio of POAF development in patients with stable angina grade III was 1,8 (95% CI 0,5-75, p=0,4), NYHA III — 0,85 (95% CI 0,2-3,5, p=0,55), history of CAD more than 20 months — 1,8 (95% CI 1,2-8,1, p=0,03), LA diameter more than 39 mm — 4,2 (95% CI 1,6-9,5, p<0,0001), allele G MMP-9 A8202G — 2,6 (95% CI 1,2-75, p=0,03).

Conclusion. In elderly patients undergoing coronary artery bypass graft surgery left atrial diameter more than 39 mm, history of coronary artery disease more than 20 months and the presence of G allele of MMP-9 A820G are significantly associated with postoperative atrial fibrillation occurrence.

Aim. To study the possibility of using the genotypes of the TBX5 gene as independent variables for predicting the development of idiopathic disorders of atrioventricular and intraventricular conduction in individuals of the East Siberian population.

Material and methods. The study involved 260 patients with idiopathic disorders of atrioventricular and intraventricular conduction and 263 people in the control group. Among patients with idiopathic cardiac conduction disorders (CCD), 71 patients had atrioventricular block (AVB), 84 patients had right His bundle branch block (RBBB) and 105 patients had left His bundle branch block (LBBB). Among patients with idiopathic CCDs 136 were men, 124 — women. The mean age of persons with CCD was 40,72±18,35 years. There were 135 men and 128 women in the control group. The mean age of the control group was 41,34±17,26 years. The patients underwent a clinical and instrumental examination (electrocardiography (ECG), echocardiography, bicycle ergometry, Holter ECG monitoring, coronary angiography, magnetic resonance imaging of the heart, myocardial scintigraphy) and molecular genetic testing of the TBX5 genotypes. Statistical processing of the material was carried out using the Excel 2010, Statistica for Windows 70 and SPSS 20 software.

Results. The AA genotype of the TBX5 gene reduces the risk of AVB in the group of women. The presence of AA and AG genotypes is a protective factor in the development of LBBB. The risk of LBBB, obtained by the method of logistic regression, was 34,3%. The resulting model predicts the absence of LBBB with a likelihood of 973%. The development of LBBB was correctly predicted in 9,3% of observations.

Conclusion. The genotypes of the TBX5 gene can be used as an independent variable to predict disorders of atrioventricular and intraventricular conduction.

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<0,05.

Results. For the assessed MNPs gene NOS1AP the following significant differences in genotypes frequencies were found: rs12567209 GG vs AA+AG OR =1,76 (CI 1,07¬2,9) p=0,026, rs3751284 CC vs CC+TT OR =0,68 (CI 0,47-0,97) p=0,037, rs12143842 CC vs CT+TT OR =0,54 (CI 0,38-0,75) p=0,0004. For alleles of the gene NOS1AP the following significant differences were found: rs12567209 A vs G OR =0,58 (CI 0,36¬0,93) p=0,025 and rs12143842 С vs T OR =0,6 (CI 0,46-0,79) p=0,0004. In further assessment it was shown that the loci rs12143842 and rs12567209 are clutched (D’ =1). In evaluation of the clutch block for rs12143842 and rs12567209 the following was found: TG vs CG+CA OR =1,64 (CI 1,25-2,16) p=0,0004.

Conclusion. MNPs (rs13184658, rs10076582, rs33862) of the gene KCNN2 and rs348624 gene NOS1AP, probably, does not play role in SCD in Novosibirsk population. rs12143842, rs12567209 and rs3751284 NOS1AP are associated with SCD. Further studies needed to assess rs12143842 and rs3751284 of gene NOS1AP, as the rs12567209 is clutched with rs12143842.

Aim. To confirm association between sudden cardiac death (SCD) and single nucleotide polymorphisms rs6582147 rs 10010305, rs2136810, rs17797829, identified as the most likely candidate markers.

Material and methods. The SCD group (n=360, mean age 53,0±9,2 years, men — 76,9%, women — 23,1%) was formed using the SCD criteria of the European Society of Cardiology. The control group (n=402, mean age 52,9±9,1 years, men — 69,7%, women — 30,3%) was selected by gender and age from the DNA bank of international studies MONICA, HAPIEE. DNA is separated by phenol-chloroform extraction. Genotyping was performed by polymerase chain reaction followed by analysis of restriction fragment length polymorphism.

Results. The GT rs6582147 genotype is associated with a protective effect on SCD (OR=0,671, 95% CI 0,496-0,909, p=0,011), and the GG genotype with an increased risk of SCD (OR=1,598, 95% CI 1,195-2,135, p=0,002). The greatest effect was in the group of men over 50 years old (p<0,05). The CT rs10010305 genotype is associated with SCD in the group of men (OR=1,773, 95% CI 1,085-2,897 p=0,027), in the group of men over 50 years old (p<0,05) and in the group of people over 50 years old without separation according to sex (OR=1,719, 95% CI 1,038-2,847 p=0,041). The GG rs2136810 genotype is associated with an increased risk of SCD (OR=1,372, 95% CI 1,005-1,871, p=0,049); in the group of people over 50, the GA rs2136810 genotype is associated with a protective effect against SCD (OR=0,642, 95% CI 0,422-0,976, p=0,045). In the group of women, the GG rs17797829 genotype is protective for SCD (OR=0,392, 95% CI 0,203-0,760, p=0,007), in the group of women over 50, except for the GG genotype, the AA genotype of the same polymorphism is associated (OR=2,739, 95% CI 2,176-3,448, p=0,020).

Conclusion. According to the results of study, single nucleotide polymorphisms rs6582147 rs10010305, rs2136810, rs17797829 confirmed the association with SCD.

Aim. To study the association of new polymorphisms with sudden cardiac death (SCD) in men.

Material and methods. The SCD group (n=278) was formed using guidelines of the World Health Organization and the European Society of Cardiology. The autopsy material was taken from the men who died suddenly outside the prevention and treatment facilities who underwent medicolegal examination according to a standard protocol. The average age in the SCD group was 53,2±8,7 years. The control group (n=274) was selected by sex and age from the DNA bank formed during the international studies of MONICA and HAPIEE. The mean age of men in the control group was 53.±8,3 years. Genomic DNA was separated from myocardial tissue and venous blood by the method of phenol-chloroform extraction. Rs10503929, rs7121, rs6730157, rs11720524, rs7737692, rs7521023 polymorphisms were tested using real-time PCR. The insertion- deletion polymorphisms rs.0692285 and rs39.7 were genotyped by PCR with flanking primers followed by polyacrylamide gel electrophoresis. Statistical analysis was performed using the SPSS 13.0 software package.

Results. By comparison the frequencies of rs7121 genotypes in the studied groups of Novosibirsk, an increase in the proportion of CC genotype carriers in the group with SCD (OR=.6, 95% CI 1,1-2,2; p=0,025) was found. The carriage of the rs.0692285 ID genotype reduces the risk of SCD (OR=0,6, 95% CI 0,4-0,9; p=0,0M). A carriage of the rs39.7 ID genotype increases the risk of SCD (OR=.5, 95% CI 1,1-2,2; p=0,020).

Conclusion. The rs7121 of the GNAS gene, the rs.0692285 of the RYR2 gene, and the rs39.7 of the COL1A2 gene are associated with SCD. Rs10503929, rs6730157, rs11720524, rs7737692, rs7521023 polymorphisms do not associate with SCD in the men of Novosibirsk.

Aim. To assess the clinical, biochemical, and genetic risk factors for the development of hepatocyte cytolysis syndrome in patients with a combination of fatty liver disease and recrudescence of chronic cardiovascular pathology.
Material and methods. The study included 74 patients with chronic cardiovascular disease (coronary heart disease, chronic heart failure, hypertension) treated in the cardiology department of the Central Clinical Hospital of the Siberian Branch of Russian Academy of Sciences with a normal baseline transaminase level (AST and ALT); 12 of them have increasing of transaminase level on 10-12 days. All patients underwent therapeutic and diagnostic procedures in accordance with the medical standards in Russian Federation. Genotyping of polymorphic loci of the genes of the cytochrome P450 family was carried out using real-time polymerase chain reaction (PCR).
Results. There was no significant correlation between cytolysis syndrome and phenotypic characteristics: gender, age, body mass index. A positive correlation of fatty liver disease with abdominal obesity and body mass index was confirmed. There was no significant correlation between cytolysis syndrome and clinical and biochemical risk factors: comorbidity and lipid profile. The presence of minor minor allele of cytochrome P-450 — CYP2C9, CYP2D6, CYP2C19 genes in a patient with fatty liver disease increases the risk of cytolysis syndrome during CVD therapy.
Conclusion. Pharmacogenetic testing of polymorphic variants of cytochrome P-450 — CYP2C9, CYP2D6, CYP2C19 genes is advisable to recommend to patients with cardiovascular diseases and high-risk of liver disorders for a personalized approach to therapy.

Aim. To study association between polymorphisms of candidate genes and the development of non-infectious and infectious endocarditis (IE).

Material and methods. During the study 175 patients were examined. They were divided into two groups: the first group — 81 patients with non-infectious endocarditis and the second one — 94 patients with IE. We present a comparative analysis of the genotype frequencies of the five genes polymorphisms: rs11697325 (-8202 A/G) of the MMP9 gene, 4a/4b of the NOS3 gene, rs4340 of the ACE gene, rs2476601 (С1858Т) of the PTPN22 gene, rs231775 (49 A/G) of the CTLA4 gene in groups of patients with endocarditis and healthy individuals.

Results. We found association between endocarditis and rs11697325 (-8202 A/G) of the MMP9 gene, 4a/4b of the NOS3 gene, as well as rs2476601 (C1858T) of the PTPN22 gene with IE.

Conclusion. Thus, association between three of the five polymorphisms and vegetations on the valvular heart apparatus was revealed.

Aim. To study relationship between the polymorphism of five polymorphic sites of EDN1, SELE, SELP, SELPLG genes with the risk of infectious endocarditis (IE) and the connection of genotypes of studied sites with concentration of the corresponding proteins in the blood.

Material and methods. The study included 208 patients with IE and 300 healthy donors. Genotyping was performed on 6 polymorphic sites of 4 genes by real-time PCR. The levels of endothelin-1, sE-selectin, sP-selectin were determined by the ELISA technique.

Results. We determined that the T allele (G/T genotype) of rs5370 polymorphic site of EDN1 gene have a risk effect on IE in the superdominant mode of inheritance (OR=1,58, 95% CI=1,05-2,35, p=0,027). At the same time, the association between levels of endothelin-1, sE and sP selectins and carriage of the variable genotypes of the corresponding genes was not found. We noted that serum concentrations of biologically active endothelial proteins differ between patients with IE and healthy individuals.

Conclusion. The study confirms the presence of endothelial dysfunction markers in the blood of patients with IE. It shows the association between rs5370 site of EDN1 gene and an increased risk of IE in heterozygous carriers of the minor T allele. However, additional research is needed to confirm these observations and to get detailed description of how gene variability determines underlying risk for IE.

Aim. To establish associations of polymorphisms of candidate genes coding for the components of the endothelial (NOS3, MTHFR) and sympathoadrenal systems (ADRB1, ADRA2B) with coronary heart disease (CHD) in the cohort of the small population of Mountain Shoriya.

Material and methods. A clinical and epidemiological study was conducted in the areas of Mountain Shoriya (Orton, Ust-Kabyrza, Sheregesh, Tashtagol). Analysis of risk factors included recording the age, sex, body mass index, waist circumference, presence/absence of arterial hypertension (AH), smoking, and the presence of disorders of lipid and carbohydrate metabolism. CHD diagnosis was made by three epidemiological criteria: coding of the electrocardiogram according to the Minnesota code, Rose questionnaire, and a history of myocardial infarction. The patient underwent molecular genetic testing. DNA isolation from blood was carried out by the method of phenol-chloroform extraction. Statistical processing was carried out using the programs STATISTICA 6.1 (StatSoft Inc., USA) and SNPStats.

Results. The prevalence of CHD in the Shoriya cohort was 9,7%. The results of our study established the relationship of genetic markers of the sympathoadrenal and endothelial systems with coronary atherosclerosis in the indigenous population of Shoriya. The high risk of atherosclerotic heart disease was associated with the 4b/4a genotype of the NOS3 gene (OR 2,57 95% CI (1,12-5,86), p=0,026) according to the dominant mode of inheritance. The relationship of the T/T genotype of the MTHFR gene with CHD by recessive inheritance was established (OR 13,28; 95% CI (1,79-98,40), p=0,024).

Conclusion. Due to genetic research, there is a real opportunity not only to carry out accurate molecular diagnostics, but also to determine an underlying risk for a disease. Detection of genetic disposition to CHD can be carried out long before the onset of clinical symptoms, which can effectively prevent its development.

Aim. To assess polymorphisms of the hemostatic system genes in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and their influence on the results of thrombendarterectomy from the branches of the pulmonary artery.

Material and methods. The study included 70 people with verified CTEPH who underwent thrombendarterectomy from the branches of the pulmonary artery. We studied the prevalence of polymorphisms of the hemostatic system genes (F2: 20210 G>A; F5: 1691 G>A (Arg506Gln); F7: 10976 G>A (Arg353Gln); F13: G>T (Val34Leu); FGB: 455 G>A; ITGA2: 807 C>T (Phe224Phe); ITGB3: 1565 T>C (Leu33Pro); SERPINE1 (PAI-1): 675 5G>4G) and their relationship with the immediate and long-term results of surgical treatment.

Results. One or several polymorphisms of the hemostasis system genes were registrated in 98% of cases in the group with CTEPH. The most common polymorphism of the SERPINE1 (PAI-1) gene was 675 5G>4G (in 80% of cases). Mutation of the F2 gene: 20210 G>A was noted in 14% of patients, F5: 1691 G>A (Arg506Gln) - 13%, F7: 10976 G>A (Arg353Gln) - 11%, F13: G> T (Val34Leu) - 34 %, FGB: 455 G> A - 35%, ITGA2: 807 C>T (Phe224Phe) - 48%, ITGB3: 1565 T>C (Leu33Pro) - 24%. The only factor influencing the results of surgical treatment was the polymorphism of the prothrombin gene (20210 G>A), which showed a high predictive value in assessing the risk of respiratory failure in the early postoperative period of thrombendarterectomy from the branches of the pulmonary artery (OR 3,5 (1,7-18,8) p=0,041). Other genetic disorders of the hemostatic system did not show significant associations with the outcome of surgical treatment.

Conclusion. We showed the relationship between the presence of prothrombin gene polymorphism (20210 G>A) and the increased risk of respiratory failure in the early postoperative period of thromboendarterectomy from the branches of the pulmonary artery. Other genetic disorders of the hemostatic system and their carriage did not show significant associations with the outcome of surgical treatment.

Aim. To determine the frequency of markers of chronic kidney disease (CKD) in hypertensive patients with high and very high cardiovascular risk, to assess relationship with the renal hemodynamics.

Material and methods. We studied 70 patients with medically-controlled hypertension (63,2±8,3 years, 48,6% male, office blood pressure (BP) was 130,5±13,7/78,1±8,5 mm Hg), 40 patients from them as part the Russian multicenter program CHRONOGRAF. Measurement of the office BP, ambulatory BP monitoring were performed. Glomerular filtration rate (GFR) was calculated using the CKD-EPI formula, and albuminuria (AU) was determined as albumin/creatinine (A/Cr) ratio in the morning portion of urine (n=40) or 24-hour urinary albumin excretion (UAE) (n=22). Intrarenal vascular resistance was estimated by renal duplex Doppler ultrasound, the resistive index (RI) levels were calculated.

Results. GFR and albuminuria were normal in 68,6% of patients with well-medically-controlled hypertension: achieved levels of office BP, BP-day and BP-night were established. Markers of CKD were detected in 31,4% of patients (GFR <60 ml/ min/1,73 m2 in 271% patients, A/Cr >30 mg/g and/or UAE >30 mg/day in 12,9%). RI in the segmental intrarenal arteries was correlated with GFR (Rs=-0,4232, p=0,0005). The levels of renal RI were higher in CKD-patients vs non-CKD-patients and those were the highest in diabetic patients. The impact of the RI values in segmental IRA to the detection of CKD markers was established during the ROC-analysis.

Conclusion. The high frequency of markers of CKD (31,4%) was identified even in patients with well-medically-controlled hypertension. The negative correlation was between GFR and RI. There were expressed disturbances of renal hemodynamics in the presence of CKD markers, especially in patients with DM2. The cut-off point RI in segmental IRA to the identification of markers of CKD is 0,725.

Past decade, there is a remarkable evidence of that the variation of DNA copies number (copy number variation, CNV) is related with onset of inborn heart defects (IHD). The review is focused on an impact of CNV in IHD development. Attention is paid on widely known variations, as the microdeletions of 22q 11 chromosome region, as the novel unique variations that were discovered recent years. We assume that common regard on causation of CNV includes a description of their part and characteristics of the pathology caused. Special place does take the analysis of candidate genes in IHD etiology and mechanisms of their pathological influence under the circumstances of gene doses change. A discussion provided on which genetic characteristics of CNV are more informing in assessment of probable pathogenicity of microstructural chromosomes recomposition.

The review article presents the state-of-the-art of use of dual antiplatelet therapy (DAPT) in patients with acute coronary syndrome (ACS) based on modern clinical guidelines and in actual clinical practice. The main differences in the frequency of use and duration of DAPT in different countries are discussed. The study included analysis of the characteristics of patients in randomized clinical trials and patients in actual clinical practice who take DATT after undergoing ACS. Literature sources from open databases PubMed, MEDLINE, eLibrary are used.

The review article study the safety and efficacy of using direct acting oral anticoagulants: thrombin inhibitor dabigatran etexilate and inhibitors Xa of the blood clotting factor apixaban, rivaroxaban and edoxaban compared with the vitamin K antagonist warfarin in patients with non-valvular atrial fibrillation. The advantage of direct oral anticoagulants is emphasized. Particular attention is paid in the article to dabigatran etexilate, which demonstrated high efficacy and safety in randomized clinical trials and in actual clinical practice in patients with non-valvular atrial fibrillation. In addition, dabigatran etexilate in the composition of dual antiplatelet therapy in patients with coronary heart disease after stenting of the coronary arteries demonstrated greater safety than triple antithrombotic therapy, which included warfarin. The article shows indications for the use of dabigatran antagonist idaruzizumab and the method of its administration.

Infectious endocarditis (IE) is a disease, usually of bacterial nature, the mortality rate from which is in fourth place among other lethal infectious diseases. In recent years there has been a tendency to an increase of prosthetic valve IE cases. The problem of antibiotic resistance leading to a decrease in the effectiveness of therapy is relevant for IE. Development task of new effective methods of preventing this disease, as well as assessing the severity of its consequences, is extremely relevant, especially because of progression of personalized medicine. The immune response plays an important role in the pathogenesis of IE, while receptors of the innate immune response are of great importance in the development and progression of this disease. Polymorphism of genes encoding these receptors leads to a change in their functional activity, which determines the effectiveness of the organism response to infection. This review analyzes the effect of polymorphism of several innate immune response receptors genes, as well as changes in their expression in patients with IE, and shows their importance in development of the individual sensitivity of patients to this pathology.

Mutations in the genes encoding desmosomal proteins cause a wide range of diseases associated with abnormalities of the skin, hair and heart. In 45-50% these mutations determine the development of arrhythmogenic right ventricular cardiomyopathy. Today, more than 120 autosomal dominant and autosomal recessive mutations of the desmoplakin (DSP) gene are known, causing skin and cardiac disorders. The article presents a rare clinical case of Carvajal syndrome (OMIM 605676), associated with compound heterozygous mutations, with the classic triad of symptoms (the phenotype of dilated cardiomyopathy, keratoderma, and woolly hair), which was first identified in Eastern Europe (Belarus). A brief literature review of the problems and issues of differential diagnosis are presented in the article in the form of a comparative analysis of Carvajal syndrome with phenotypically similar pathology - Naxos syndrome, caused by mutations in the gene encoding another desmosomal protein - Placoglobin (Naxos syndrome, OMIM 601214), and leading to the development of arrhythmogenic right ventricular cardiomyopathy.