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.

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.

Objective. To analyze autonomic regulation in patients with orthostatic hypotension (OH), vasovagal syncope (VVS) and postural orthostatic tachycardia syndrome (POTS) compared to healthy individuals. Material and methods. Seventy-two patients were included: 11 ones with neurogenic OH, 46 ones with isolated VVS and 15 ones with VVS combined with POTS. Diagnosis was based on clinical data and tilt test. The control group consisted of 28 healthy volunteers without previous syncope or any chronic diseases. We analyzed autonomic regulation in supine resting position (heart rate variability, systolic and diastolic blood pressure, spontaneous baroreflex sensitivity) and under provocative tests (Valsalva-Weber maneuver, deep breathing, hand grip isometric test, and tilt test). To study hemodynamic and vegetative parameters, we used a rheograph-polyanalyzer RGPA-6/12 with software “REAN-POLY” (MEDIKOM-MTD) and specialized complex “Cardiotechnics SAKR” (INKART). Results. Patients with OH were characterized by reduced blood pressure (BP) at initial stage of tilt test, weak pressor response during hand grip isometric test and attenuated BP response in Valsalva maneuver compared to patients with isolated VVS, POTS and healthy individuals. In addition, patients with OH had lower spontaneous baroreflex sensitivity and significant suppression of respiratory sinus arrhythmia. Patients with isolated VVS had no significant differences in hemodynamic parameters and autonomic control when compared with healthy individuals. Patients with POTS had less pronounced BP increment in hand grip isometric test and Valsalva maneuver compared to healthy individuals and patients with isolated VVS. Individual analysis with reference data from healthy individuals revealed multiple (7—14 parameters) autonomic dysfunctions in all 11 patients with OH. Deviations from normal range in at least one parameter were detected in 14 (93%) patients with POTS, and 10 (67%) patients had deviations in ≥ 3 parameters. Autonomic dysfunctions were recorded in 33 (71.7%) out of 46 patients with VVS, and 14 (30.4%) patients had deviations in ≥ 3 parameters. Conclusions. A comprehensive assessment of hemodynamic parameters and autonomic regulation at rest and in functional tests reveals multiple abnormalities in blood pressure and heart rate control systems in all patients with OH manifested by insufficient vasoconstrictor response to preload reduction and reduced baroreflex and respiratory modulation of sinus node. Individual analysis identifies autonomic dysfunctions in 71.7% of patients with isolated VVS and in 93% of patients with VVS combined with POTS.

Состояние барорефлекторной регуляции у больных с ортостатической гипотензией, вазовагальными обмороками и синдромом постуральной ортостатической