Vasovagal Syncope Is Associated with Variants in Genes Involved in Neurohumoral Signaling Pathways

Abstract

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.

Novel risk patterns of vasovagal reactions in NZ blood donations complicated by COVID-19 restrictions

“…Such factors likely interact with the identified risk factors ( 31 , 32 ) but probably in rather complicated ways that require well-designed large studies to tease out how they might interplay in triggering iVVRs. Second, while mechanisms regulating iVVR risk remain obscure, developing strategies for early screening and/or intervention ( 2 , 24 ) can not only effectively mitigate iVVR risk but also help dissect the causal mechanisms by studying any genetic ( 10 , 22 ) and/or epidemiological differences in iVVR cases that do not respond to interventions.…”

“…Other risk factors include anthropometric measures such as low body mass index and low estimated blood volume ( 15 ), psychological factors like fear of blood drawn and pain ( 15 , 16 ), contextual factors such as inexperienced phlebotomists ( 17 , 18 ) and collection site settings related to long waiting and/or bleeding time ( 19 ). Intriguingly, previously assumed genetic risk factors such as history ( 20 ) particularly familial history ( 21 ) of vasovagal syncope have received renewed interest ( 10 , 22 ), and may add a missing piece of the puzzle of VVR causal mechanisms that however remain largely obscure. Therefore, implementation of VVR intervention and prevention measures [e.g., pre-donation water loading and applied muscle tension ( 2 )] would be sensible and effective approaches at this stage ( 23 , 24 ).…”

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“…Additionally, there are novel lines of research based on translational research, which aim, through the identification of polymorphisms, to categorize the existence of phenotypes resistant or responsive to specific therapies, which would help to describe new pathophysiological mechanisms and to design new therapeutic targets (44)(45)(46)(47)(48)(49)(50). It can be stated that it is a current issue about which not much is known and on which the sociodemographic, clinical, and genotype characterization of the affected population depends greatly.…”