Aim. To assess the rs2285666 nucleotide sequence of the angiotensin-converting enzyme 2 (ACE2) gene and its association with acute coronary syndrome (ACS) in patients after coronavirus disease 2019 (COVID-19).

Material and methods. The study included 100 patients after COVID-19, including 50 men and 50 women, hospitalized with a diagnosis of ACS. The diagnosis of COVID-19 in all 100 patients was confirmed by a positive polymerase chain reaction (PCR) smear. All patients underwent percutaneous transluminal coronary angioplasty with stenting, standard clinical and paraclinical examination, and genetic testing of the rs2285666 ACE2 gene by PCR followed by restriction fragment length polymorphism analysis. The comparison group consisted of 200 patients with ACS after COVID-19, confirmed by a PCR smear or antibody titer.

Results. Statistically significant differences were obtained for the AA genotype, carriage of which among male patients with ACS after COVID-19 was 2,5 times less common than in men in the control group (OR =0,391, 95% CI: 0,167-0,917; p=0,028). On the other hand, carriage of the rs2285666 GA genotype of the ACE2 gene is not associated with an increased risk of ACS in women after COVID-19. There were no significant differences in genotype frequencies in the group of women and in the general group (without division by sex).

Conclusion. The data obtained may indicate a protective role of the rs2285666 AA genotype of the ACE2 gene for males regarding ACS development after COVID-19. These results are the first steps towards building a prognostic model to estimate the ACS risk in patients after COVID-19, which will reduce morbidity and mortality for this group of patients.

Aim. To identify anthropometric parameters that are associated with a more frequent development of dilated cardiomyopathy (DCM) in patients with rs1805124 and rs35068180 polymorphisms.

Material and methods. The present study included 111 patients with idiopathic dilated cardiomyopathy (DCM) (99 men (89,2%) and 12 women (10,8%)). The mean age of the participants was 51±9,1 years, with an age range of 20 to 69 years. The control group included 101 healthy individuals (mean age, 50,8±12,3 years; age range, 34 to 79 years (men, 86,1%)).

The Rees-Eysenck index (body length*100/chest transverse diameter*6) and the Tanner's sexual dimorphism index (3*shoulder diameter–intercrestal diameter) were used.

In addition to the conventional body mass index (BMI), the study determined waist circumference, hip circumference, body shape index (BSI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), body adiposity index (BAI), body roundness index (BRI).

Results. Patients carrying the GG genotype had significantly higher WHR, BAI, and BRI indices compared to the control group. However, similar differences were also observed among carriers of the AG and AA genotypes. Also, carriers of the AG and AA genotypes of the rs1805124 polymorphism significantly differed from the control group in WHR and WHtR. This may indicate the primary influence of somatometric indices, rather than the studied polymorphisms, on the DCM development.

The multivariate analysis performed using the Wald stepwise selection method showed a significant effect of BRI (p=0,000) and the Rees-Eysenck index (p=0,000) on the development of DCM in carriers of the rs1805124 polymorphism GG genotype. In patients carrying the 6a/6a genotype, the WHtR, WHR, BMI, BAI, and BRI were significantly higher than in the control group. Similar differences were also observed among carriers of the 6a/5a genotype. The indices of WhtR, BAI, BMI, and BRI were significantly higher in carriers of the 5a/5a genotype. However, similar differences were also observed among carriers of the AG and AA genotypes. Also, carriers of the AG and AA genotypes of the rs1805124 polymorphism significantly differed from the control group in both WHR and WHtR.

Conclusion. Most likely, such somatometric indices as BRI, WHR, WHtR, BAI, and BMI are of great importance in the development of DCM. In carriers of the homozygous rare allele G of the rs1805124 polymorphism, independent predictors of DCM may be BRI and the Rees-Eysenck index, while in carriers of the rare allele 5a of the rs35068180 polymorphism — BRI, BMI, and the Rees-Eysenck index. However, BRI and the Rees-Eysenck index may be independent predictors of DCM regardless of the genotypes of the studied polymorphisms.

Aim. To determine the prevalence and profile of rare variants of the filamin C gene (FLNC) among patients with hypertrophic obstructive cardiomyopathy (HCM) referred for septal myectomy, and to provide a clinical description of HCM occurring with these variants.

Material and methods. Ninety-eight adult patients with HCM who underwent septal myectomy underwent genetic testing by next-generation sequencing using a targeted cardiac panel (39-gene panel in 58 patients and 17-gene panel in 40 patients). In patients with rare FLNC variants (with a minor allele frequency <0,01%), the data of anamnesis, echocardiography, electrocardiography, Holter monitoring, and myocardial histological examination were analyzed.

Results. Four patients with rare FLNC variants (two men and two women) were identified, which amounted to 4% (Pro1774Ser, Thr1317Pro and His1834Tyr, the latter was detected twice). These variants were missenses and classified as variants of uncertain clinical significance. The FLNC p.Thr1317Pro variant in one patient was combined with a pathogenic variant p.Val606Leu in MYH7 gene. All patients received diagnosis of HCM after age of 40 years. Clinical course was represented by mild symptoms of heart failure and class II stable angina. Episodes of non-sustained ventricular tachycardia, atrial fibrillation or clinically significant conduction block were not registered. One patient with p.His1834Tyr FLNC variant had reverse curve interventricular septum morphology, whereas other patients had predominant hypertrophy of basal segment of interventricular septum. Diastolic dysfunction did not exceed grade 1-2 in all four patients.

Conclusion. The clinical characteristics of carriers of rare FLNC variants in our study did not differ from the majority of patients with HCM who underwent septal myectomy. Rare FLNC variants can act as causative or modifying factors of HCM course. Functional and population-based studies using segregation analysis should clarify the pathogenicity of rare FLNC variants.

Aim. To identify the predictors of poor prognosis in patients with pulmonary embolism (PE).

Material and methods. The study included 120 patients with verified PE. The analysis included the clinical evidence collection, paraclinical investigations (including echocardiography) and genetic analysis. Cox regression analysis was used to assess mortality predictors. Statistical data processing was performed using Excel 2019, SPSS Statistica v. 26 (IBM, USA), MedCalc v. 20.104 and JMP Pro 17 (SAS, USA) software.

Results. The following independent mortality predictors were identified using multivariate regression analysis: age (odds ratio (OR) 1,051, p=0,0002), prior venous thromboembolism (OR 2,090, p=0,0117), TT genotype of the F13A1 rs5985 polymorphism (OR 2,820, p=0,0427) and anteroposterior right ventricular size (OR 1,043, p=0,0294). Right ventricular wall hypokinesis (OR 5,040, p=0,0285), submassive pulmonary artery involvement (OR 2,714, p=0,0025), prior myocardial infarction (OR 2,839, p=0,0028) and other factors were significantly associated with an increased death risk. Based on these predictors, a prognostic model was developed that allows for effective stratification of the death risk.

Conclusion. The predictors identified in the study can be used for risk stratification and optimization of patient management with PE, which can improve the prognosis and treatment outcomes.

Aim. To study the involvement of APOC1 rs445925 and rs4420638 single nucleotide polymorphisms (SNP) in the development of occlusive peripheral arterial disease (PAD) of lower extremities.

Material and methods. The study included 1278 people, including 630 patients with occlusive PAD and 648 relatively healthy individuals. Genotyping of APOC1 rs445925 and rs4420638 SNPs was performed using the MassARRAY-4 genomic mass spectrometer. The analysis of the association of alleles, genotypes, haplotypes and diplotypes with the risk of occlusive PAD was performed using the statistical programs SNPStats, PLINK, v1.9 and STATISTICA 13.3. The adaptive permutation test was used to assess statistical significance of associations (P_perm).

Results. The rs445925-A (P_perm=1,0×10^-6) and rs4420638-G (P_perm=0,006) alleles, as well as the rs445925-G/A-A/A (P_perm=1,0×10^-6) and rs4420638-A/G-G/G (Pperm=0,006) genotypes were associated with an increased risk of occlusive PAD. The rs445925 polymorphism was also associated with the blood cholesterol level in patients with occlusive PAD (P_perm=0,04). The rs445925A-rs4420638A and rs445925A-rs4420638G haplotypes, as well as three APOC1 diplotypes, showed a pronounced relationship with a predisposition to occlusive PAD. In particular, the rs445925G/A×rs4420638A/A (odds ratio (OR) 6,59, 95% confidence interval (CI) 4,20-10,35, P=2,4×10^-19) and rs445925G/A×rs4420638A/G (OR 4,24, 95% CI 2,23-8,03, P=2,0×10^-6) diplotypes were associated with an increased risk of occlusive PAD. The rs445925G/G×rs4420638A/A diplotype had a protective effect on the disease development (OR 0,26, 95% CI 0,20-0,35, P=1,3×10^-20). Associations of haplotypes with the severity of peripheral arterial stenosis of various locations were also revealed (P<0,05).

Conclusion. The study results established for the first time that APOC1 rs445925 and rs4420638 polymorphic variants are part of a genetic predisposition to occlusive PAD and have a significant effect on the severity of peripheral arterial stenosis. The molecular mechanisms underlying the identified genotypic associations can affect not only lipid metabolism disorders, but also the proliferation of immunocompetent cells, platelet activation and aggregation processes, inflammation and apoptosis.

Aim. To study the effect of EDNRA rs6842241 and MRAS rs9818870 polymorphic variants on the lipid-lowering effect of rosuvastatin in patients with coronary artery disease (CAD), and to determine the role of these loci in the development of CAD among Central Russia residents.

Material and methods. The pharmacogenetic study involved 116 patients with class II-III stable angina. Patients received rosuvastatin with dose titration to achieve target low-density lipoprotein cholesterol (LDL-C) levels. The genetic and epidemiological study included DNA samples of 1960 Central Russia residents (1261 patients with CAD and 699 healthy individuals). Genotyping of polymorphic variants was performed on a MassARRAY-4 genomic mass spectrometer. Associations of polymorphisms with lipid changes for 1, 6 and 12 months of follow-up were calculated using linear regression analysis adjusted for sex, age, body mass index and rosuvastatin dose; associations with CAD risk — using logistic regression analysis adjusted for sex and age. The statistical significance of associations was calculated using the permutation test.

Results. Carriage of the AA and CA genotypes of EDNRA rs6842241 variant was associated with a weakening of the rosuvastatin lipid-lowering effect in relation to total cholesterol (β=0,075, p=0,001) and LDL-C (β=0,145, p=0,017) at the end of the first month and 12 months of therapy (β=0,049, p=0,013 and β=0,072, p=0,040, respectively). Carriage of the AA genotype of EDNRA rs6842241 variant was associated with an increased CAD risk (odds ratio 5,36; 95% confidence interval 1,62-17,71, p=0,004). MRAS rs9818870 variant was not associated with rosuvastatin pharmacogenetics or with the CAD risk. Both polymorphic variants were not associated with lipid levels outside of lipid-lowering therapy, as well as with the triglyceride changes. High-density lipoprotein cholesterol levels during the entire follow-up period changed insignificantly.

Conclusion. The EDNRA rs6842241 variant is associated with both a weakening of the lipid-lowering effect of rosuvastatin in CAD and an increased risk of its development in the population.

Aim. To study the expression level of the P-selectin gene (SELP) mRNA and the level of intercellular interaction in patients with coronary artery disease (CAD) before and after coronary artery bypass grafting (CABG) in patients with resistance to acetylsalicylic acid (ASA).

Material and methods. The study included 65 patients with CAD who were scheduled to CABG. SELP expression, the platelet-leucocyte aggregate level, and the level of P-selectin expression on aggregates were determined in all participants. Resistance to ASA was defined as platelet aggregation with arachidonic acid ≥20% in at least one sample. All studies were performed before and on the 8^th-10^th day after CABG.

Results. Among patients, 29,4% (n=30) were resistant to ASA (ASA-R) at least at one point, while 7,8% (n=8) acquired resistance after CABG. ASA-R had a higher level of SELP (0,41 [0,28; 0,48] vs 0,32 [0,23; 0,39], p=0,037), absolute content of monocyte-platelet aggregates (24,70 [9,69; 39,90] vs 10,15 [5,27; 30,63], p=0,037) and relative amount of platelet-platelet CD62P aggregates (7,37% [3,43; 35,49] vs 4,84% [0,90; 9,63], p=0,045). A negative correlation was found between SELP expression and the relative content of monocyte-platelet aggregates (ρ=-0,349, p=0,013) on days 8-10 after CABG. Mmultivariate regression analysis found that the level of SELP gene mRNA expression is a predictor of ASA resistance before CABG (odds ratio 404,48; 95% confidence interval 1,68-97461,63).

Conclusion. Increased SELP expression is associated with an increase in platelet aggregation activity, which contributes to an insufficient platelet response to antithrombotic therapy in patients with CABG. The level of SELP gene mRNA expression can be considered as a predictor of ASA resistance.

Aim. To evaluate the efficacy of P2Y₁₂ receptor inhibitors (clopidogrel and ticagrelor) in patients with myocardial infarction (MI) living in the northern region of Russia (Khanty-Mansi Autonomous Okrug — Yugra), depending on the carriage of various CYP2C19 allelic variants.

Material and methods. This prospective observational study included 218 patients with acute MI who underwent percutaneous coronary intervention (PCI). The patients also underwent determination of allelic variants of the CYP2C19 gene. Patient were divided into groups receiving clopidogrel (n=164, 75%) and ticagrelor (n=54, 25%). Using biostatistical analysis methods, a comparison of clinical and genetic characteristics was performed, as well as an assessment of the risk of ischemic events between the groups in the long-term (108 months, 9 years) post-infarction period.

Results. Reduced (*1/*2, *2/*2, *1/*3) and increased (*1/*17, *17/*17) metabolizer CYP2C19 genotypes, as well as severe comorbidity, are reliable independent predictors of composite outcome (cardiovascular death, recurrent acute coronary syndrome, coronary stent/bypass thrombosis, myocardial revascularization, acute ischemic cerebrovascular accident) during a long-term (9 years) follow-up. The advantages of ticagrelor over clopidogrel in terms of the effect on the incidence of ischemic events in the long-term period were established without a significant difference for bleeding both in the general cohort of patients and among carriers of CYP2C19 allelic variants (*1/*2, *2/*2, *1/*3) and (*1/*17,*17/*17) in patients with MI.

Conclusion. Ticagrelor is significantly more effective than clopidogrel in reducing the risk of ischemic events in the general cohort of patients, as well as in carriers of reduced (*1/*2, *2/*2, *1/*3) and increased (*1/*17, *17/*17) metabolizer CYP2C19 genotypes during 9-year follow-up after the index MI.

Aim. To study the association of rs2232228 (HAS3 gene), rs2229774 (RARG gene), rs1056892 (CBR3 gene), rs1786814 (CELF4 gene), rs1695 (GSTP1 gene), rs8187710 (ABCC2 gene), rs7853758 (SLC28A3 gene), rs243865 (MMP­2 gene), rs243866 (MMP­2 gene), rs35068180 (MMP­3 gene), rs522616 (MMP­3 gene), rs679620 (MMP­3 gene), rs17576 (MMP­9 gene), rs3918242 (MMP­9 gene) with the probability of early doxorubicin cardiotoxicity signs in patients with breast cancer of moderate and low HFA-ICOS risk groups.

Material and methods. The study included 100 patients (women, over 18 years old) diagnosed with breast cancer who received chemotherapy using doxorubicin.

To identify early cardiotoxicity signs, echocardiography was performed before, immediately after and 12 months after the end of chemotherapy. The status of polymorphic variants of the studied genes was determined by real-time polymerase chain reaction.

Results. Based on the decrease in global longitudinal myocardial strain (>12%) immediately after and 12 months after the end of chemotherapy, the patients were divided into two following groups: A — early signs of myocardial dysfunction can be diagnosed after the end of chemotherapy (19%); B — early signs of myocardial dysfunction are detected for the first time only 12 months after the chemotherapy end (17%). In patients from category A, a number of allelic variants and genotypes with potential as independent factors for predicting the early signs of myocardial dysfunction were identified, with an emphasis on targets involved in metabolism and detoxification of doxorubicin and its derivatives. In category B, the greatest differences in the frequencies of allelic variants and genotypes were found among target genes encoding matrix metalloproteinases involved in the processes of response to the intensification of oxidative stress caused by doxorubicin and its derivatives.

Conclusion. In total, patients in the low- and moderate-risk groups can be divided into at least 2 categories based on molecular genetic testing. For these categories, the development of early signs of doxorubicin-related myocardial dysfunction before the start of chemotherapy can be predicted.

Aim. To identify single nucleotide polymorphisms reliably associated with cardiovascular toxicity in oncohematological patients receiving antitumor immunochemotherapy.

Material and methods. For the study, 34 patients with an established diagnosis of non-Hodgkin's B-cell follicular lymphoma were prospectively selected at the Clinic of the Samara State Medical University, who were indicated for antitumor immunochemotherapy according to the R-CHOP protocol. During the follow-up, the patients were divided into 2 following groups: the main group consisted of 12 patients with cardiovascular toxicity (mean age, 42,4 (2,8) years, including men — n=3 (25%)), the control group — 22 patients without cardiovascular toxicity (mean age, 39,8 (1,7), including men — n=8 (36%)). Cardiovascular toxicity was verified on the basis of a combination of specific cardiological complaints with a decrease in the left ventricular ejection fraction >10% from the baseline or in absolute terms less than 53% and/or a decrease in the left ventricular longitudinal systolic strain >12% from the baseline and/or an increase in NT-proBNP >125 pg/ml.

Results. The study presents the identified genetic features in oncohematological patients in the context of cardiovascular toxicity. ABCC5 rs1879257, PRKAG2 rs13224758, RYR2 rs10925391 and SLC22A7 rs414917 variants had a significant association with an increased risk of cardiovascular toxicity in the target group of patients by 5-6 times. In addition, the ABCB1 rs2032582 variant showed the opposite effect and was associated with a reduced risk of cardiovascular complications, having a protective effect on the cardiovascular system.

Conclusion. Although further studies are needed to confirm the diagnostic and prognostic significance of the detected genetic variants, the study results indicate the prospects of genetic screening before antitumor immunochemotherapy as a future tool for stratifying oncohematological patients and minimizing cardiovascular toxicity.

Aim. To study the distribution of somatometric indicators and indices of patients with Wolff-Parkinson-White (WPW) syndrome.

Material and methods. All patients underwent following clinical and paraclinical investigations: electrocardiography (ECG), Holter ECG monitoring, echocardiography. In addition, we performed somatometric study according to the standard method of V.V. Bunak. The main group consisted of 200 patients with WPW syndrome (men, n=97 (32,6±9,4 years); women, n=103 (47,92±11,6 years)).

Results. Anthropometry performed according to James Tanner revealed that in the general group of WPW syndrome individuals, mesomorphs prevailed (57%). A similar pattern was observed both in the groups of women (25,5%) and men (31,5%). According to the Rees-Eysenck index, the general group of WPW syndrome individuals, normosthenics (37%) and pyknics (38%) prevailed. However, in the group of women, normosthenics prevailed (24%), and in the group of men, pyknics (23,5%). The relationship analysis using Pearson's chi-squared test revealed the following: in the group of women, the WPW syndrome was moderately correlated with the thigh fat fold (0,52), and in the group of men — with the abdominal fat fold (0,56).

Conclusion. Somatometric study, taking into account the indices (J. Tanner, Rees-Eysenck), confirms the relationship between the risk of cardiovascular diseases and overweight. This can be useful for taking preventive measures in relation to groups of people with certain anthropometric features, when assessing the risk of arrhythmias within the concept of personalized medicine.

Medication adherence is a key factor of effective stroke prevention in patients with atrial fibrillation receiving oral anticoagulant therapy. At the same time, patient compliance can significantly decrease over time, which leads to an increased thromboembolism risk. A number of studies have shown that a large number of patients receiving anticoagulant therapy are insufficiently adherent to therapy (according to various sources, from 30 to 50% of patients do not comply with the prescribed treatment regimen or interrupt therapy).

Independent risk factors for non-compliance include younger age, old age, prior stroke, male sex, multimorbidity, polypharmacy. The risk of decreased compliance with double drug intake compared to single one is noted separately.

The review aim is to study the risk factors for non-adherence to oral anticoagulants in patients with atrial fibrillation and possible measures for its prevention.

Currently, natriuretic peptides (including brain natriuretic peptide (BNP)) are widely used in clinical practice as biomarkers for various cardiovascular diseases. Study of the structure and function of NPPA-NPPB locus can help to better identify patients at risk of future cardiovascular diseases, in particular heart failure.

Cardiovascular diseases (CVDs) are the leading cause of death in the world. Studies on the molecular genetic mechanisms aimed at detecting pathogenetically significant molecular targets, as well as searching for informative biomarkers remain relevant. Some of these predictive/prognostic marker candidates are the OLR1 gene products and polymorphisms.

The OLR1 gene encodes the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), the expression of which increases in response to proinflammatory or proatherogenic factors. LOX-1 plays an important pathogenetic role in the development of CVD and type 2 diabetes. Single nucleotide polymorphisms in the OLR1 gene can be used as a genetic biomarker predicting the CVDs, necessary for stratification of patients into risk groups within the concept of personalized medicine, as well as potential therapeutic targets for patients with certain clinical phenotypes. This review examines the main genetic and epidemiological studies of the OLR1 gene association with CVDs and the etiopathogenetic mechanisms of the OLR1 gene influence on their development.