Syncope, defined as a transient loss of consciousness caused by transient global cerebral hypoperfusion, affects 30–40% of humans during their lifetime. Vasovagal syncope (VVS) is the most common cause of syncope, the etiology of which is still unclear. This review summarizes data on the genetics of VVS, describing the inheritance pattern of the disorder, candidate gene association studies and genome-wide studies. According to this evidence, VVS is a complex disorder, which can be caused by the interplay between genetic factors, whose contribution varies from monogenic Mendelian inheritance to polygenic inherited predisposition, and external factors affecting the monogenic (resulting in incomplete penetrance) and polygenic syncope types.

Frequencies of the carriership of alleles and genotypes of functionally important polymorphous loci of some inflammation genes (proinflammatory cytokine genes IL-6, LTA, and TNF; anti-inflammatory cytokine gene TGFB1; and CC chemokine receptor 5 gene CCR5) were analyzed in 199 ethnic Russian patients with myocardial infarction (MI) and in a control group of 142 persons of the same ethnic descent. Complex analysis by the APSampler algorithm revealed associations of MI with the carriership of all polymorphic variants either regarded as individual risk factors (insertion-deletion polymorphism of CCR5 and SNP G252A LTA) or in combination with other alleles or genotypes. The carriership of bi-or triallelic combinations was associated with MI more reliable than the carriership of any subsets: single alleles or allele pairs. The protective triallelic combination d*CCR5 + 252G*LTA + -174C*Il-6 was found to be the most significant (p = 0.0006, OR = 0.23, CI = 0.090–0.56). Separate analysis of genetic susceptibility to MI in men and women demonstrated sexual dimorphism for the CCR5 gene.

Vasovagal syncope (VVS) is the most common cause of sudden loss of consciousness. VVS results from cerebral hypoperfusion, due to abnormal autonomic control of blood circulation, leading to arterial hypotension. It is a complex disease, and its development is largely associated with genetic susceptibility. Since abnormal neurohumoral regulation plays an important role in VVS development, we analyzed the association of VVS with polymorphic variants of ADRA1A, ADRB1, HTR1A, ADORA2A, COMT, and NOS3 genes, the products of which are involved in neurohumoral signaling, in patients with a confirmed VVS diagnosis (157 subjects) and individuals without a history of syncope (161 subjects). We were able to identify the associations between VVS and alleles/genotypes ADRA1A rs1048101, ADRB1 rs1801253, ADORA2A rs5751876, and COMT rs4680, as well as NOS3 rs2070744 in biallelic combination with COMT rs4680. Thus, we are the first to observe, within a single study, the role of the genes that encode α- and β-adrenergic receptors, catechol-O-methyltransferase, adenosine receptors and nitric oxide synthase in VVS development. These findings demonstrate that the genes involved in neurohumoral signaling pathways contribute to the formation of a genetic susceptibility to VVS.

Rationale. Cardiovascular diseases remain the leading cause of human death in the world. Studying the role of regulatory non-coding RNAs, which include short single-stranded miRNA molecules, allows a more detailed understanding of the pathological processes underlying the progression of atherosclerosis. Objective to compare the levels of circulating miRNAs in patients with coronary heart disease, confirmed by multislice computed tomography-coronarography (MSCT-CA), with risks of cardiovascular complications and clinical and demographic characteristics. To compare the profiles of circulating miRNAs in groups of patients with stable and unstable atherosclerotic plaques. Methods. MicroRNA levels in the plasma of peripheral blood of patients with coronary heart disease were determined using the miScript miRNA PCR Array MIHS-105Z kit (Qiagen). The significance of differences in miRNA levels between the compared groups was determined using the MannWhitney U-test. The correlations of the levels of circulating miRNAs with clinical and demographic parameters were evaluated using the Spearman correlation coefficient. Risk assessment of cardiovascular complications in these patients was carried out using validated scales (ACC/AHA, Framinghm, SCORE, MESA). Atherosclerotic plaque stability was evaluated using MSCT-CA. Results. The study showed a significant (p 0.05) decrease in miR-16, miR-211, miR-195 miRNA levels in the plasma of patients with coronary heart disease, which correlated with an increase in cardiac vascular risk (CVR) according to ACC/AHA, Framingham and MESA. When comparing groups of patients with stable and unstable atherosclerotic plaques, the latter revealed an increase in the level of let-7b-5p circulating microRNA (p 0.05). Conclusion. Significant associations of the three studied microRNAs with the estimated risk of CVR were identified. It is important to find circulating let-7b-5p in a group of patients with unstable atherosclerotic plaques. Correlations were established between the levels of circulating microRNAs and clinical and demographic characteristics of patients. The study shows the involvement of some microRNAs in the regulation of atherosclerosis.

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system of polygenic nature, characterized by focal inflammation, demyelination and neurodegeneration. The clinical course of MS is characterized by great heterogeneity. The consistency of the clinical forms of MS in families indicates the involvement of genomic variation in the development of the clinical phenotype. Identifying the genetic basis of MS progression may not only explain the nature of the observed clinical heterogeneity but also contribute to the development of new tools for appropriate prognosis and personalized treatment of the disease. To describe the clinical course of MS, disease severity scores are used; they characterize the degree (speed) of MS progression. The most important methods for assessing the severity of MS are based on the Multiple Sclerosis Severity Score (MSSS) and Age-Related Multiple Sclerosis Severity Score (ARMSS) scales. This review summarizes the data on the contribution of polymorphic genetic variants to MS severity as assessed by the MSSS and ARMSS scales. These data were obtained using the "candidate gene" method and genome-wide association studies.

Atrial fibrillation (AF) is one of the most common arrhythmia that occurs in patients with cardiovascular diseases. Congenital forms of AF are quite rare. Many studies have shown that genetic, epigenetic and transcription factors may play an important role in the development and the progression of AF. In our review, studies have been conducted on the identification of mutations in ionic and non-ionic channels, possibly associated with AF. These mutations were found only in isolated groups of patients with AF, and in general, monogenic forms of AF are a rare subtype of the disease. Genomic association studies have helped to identify potential links between single nucleotide polymorphisms and AF. The risk of AF in the general population is likely to be determined by the interaction between environmental factors and many alleles. In recent years, the emergence of a genome-wide associative studies has significantly expanded the understanding of the genetic basis for the inheritance of AF and has led to the emergence of new evidence of the important role of genetic factors in the development of AF, in the risk stratification of AF and the recurrence of AF. Epigenetic factors are also important in AF. Epigenetic therapy aimed at treating a disease through exposure to epigenome is currently under development. A newly emerged area of ablatogenomics includes the use of genetic profiles that allow assessing the likelihood of recurrence of AF after catheter ablation. The results of genetic studies in AF show that, in addition to their role in the appearance of congenital heart pathologies, transcription factors play an important role in the pathogenesis of AF.