The Search for the Genes of Vasovagal Syncope

Overview

Journal Front Cardiovasc Med

Specialty Cardiology & Vascular Diseases

Date 2019 Dec 19

PMID 31850372

Citations 10

Authors

Robert S Sheldon

Roopinder K Sandhu

Affiliations

Soon will be listed here.

Abstract

Only humans faint, and not all do so. Syncope tends to recur, and the predisposition to syncope can persist over many decades. Observations such as these have suggested that there may be a genetic predisposition to vasovagal syncope. It seems to have a high prevalence in some families; having a parent who faints increases the likelihood of an offspring fainting, and this is increased even further if both biological parents faint. Numerous studies have correlated a number of genotypes with positive tilt tests. However, the control subjects are usually those who faint, but have negative tilt tests, making the conclusions about association with the clinical phenotype less certain. Twin studies, highly focused genome-wide association studies, and gene duplicate studies all suggest there are sites in the genome that associate with vasovagal syncope, although the specific genes, pathways, and proteins are unknown. A recent large, candidate gene study of kindreds with high, multigenerational prevalence of the vasovagal syncope identified 3 genes that associate with vasovagal syncope. Our understanding of the genetic correlates of vasovagal syncope is in its infancy, with much to be understood.

Citing Articles

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Global prevalence of vasovagal syncope: A systematic review and meta-analysis.

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Ganglionated Plexus Ablation Procedures to Treat Vasovagal Syncope.

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Development of a nomogram model to predict malignant vasovagal syncope in Chinese children.

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

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References

Serletis A, Rose S, Sheldon A, Sheldon R . Vasovagal syncope in medical students and their first-degree relatives. Eur Heart J. 2006; 27(16):1965-70. DOI: 10.1093/eurheartj/ehl147. View

Kleinknecht R, Lenz J, Ford G, DeBerard S . Types and correlates of blood/injury-related vasovagal syncope. Behav Res Ther. 1990; 28(4):289-95. DOI: 10.1016/0005-7967(90)90080-3. View

Klein K, Berkovic S . Genetics of vasovagal syncope. Auton Neurosci. 2014; 184:60-5. DOI: 10.1016/j.autneu.2014.03.008. View

Marquez M, Urias K, Hermosillo A, Jardon J, Iturralde P, Colin L . Familial vasovagal syncope. Europace. 2005; 7(5):472-4. DOI: 10.1016/j.eupc.2005.05.004. View

Horiuchi J, Atik A, Iigaya K, McDowall L, Killinger S, Dampney R . Activation of 5-hydroxytryptamine-1A receptors suppresses cardiovascular responses evoked from the paraventricular nucleus. Am J Physiol Regul Integr Comp Physiol. 2011; 301(4):R1088-97. DOI: 10.1152/ajpregu.00144.2011. View

Theodorakis G, Leftheriotis D, Livanis E, Flevari P, Karabela G, Aggelopoulou N . Fluoxetine vs. propranolol in the treatment of vasovagal syncope: a prospective, randomized, placebo-controlled study. Europace. 2006; 8(3):193-8. DOI: 10.1093/europace/euj041. View

Tan M, Ho Y, Chin A, Saedon N, Zainal Abidin I, Chee K . Ethnic differences in lifetime cumulative incidence of syncope: the Malaysian elders longitudinal research (MELoR) study. Clin Auton Res. 2019; 30(2):121-128. DOI: 10.1007/s10286-019-00610-2. View

Lelonek M, Pietrucha T, Matyjaszczyk M, Goch J . A novel approach to syncopal patients: association analysis of polymorphisms in G-protein genes and tilt outcome. Europace. 2008; 11(1):89-93. DOI: 10.1093/europace/eun277. View

Sheldon R, Grubb 2nd B, Olshansky B, Shen W, Calkins H, Brignole M . 2015 heart rhythm society expert consensus statement on the diagnosis and treatment of postural tachycardia syndrome, inappropriate sinus tachycardia, and vasovagal syncope. Heart Rhythm. 2015; 12(6):e41-63. PMC: 5267948. DOI: 10.1016/j.hrthm.2015.03.029. View

10.

Sorrentino S, Forleo C, Iacoviello M, Guida P, DAndria V, Favale S . Lack of association between genetic polymorphisms affecting sympathetic activity and tilt-induced vasovagal syncope. Auton Neurosci. 2010; 155(1-2):98-103. DOI: 10.1016/j.autneu.2010.01.002. View

11.

Mudrakova K, Mitro P, Salagovic J, Habalova V, Kirsch P, Tkac I . Gene polymorphisms of renin angiotensin system and serotonin transporter gene in patients with vasovagal syncope. Bratisl Lek Listy. 2009; 110(2):73-6. View

12.

Hernandez-Pacheco G, Gonzalez-Hermosillo A, Murata C, Yescas P, Espinola-Zavaleta N, Martinez M . Arg347Cys polymorphism of α1a-adrenergic receptor in vasovagal syncope. Case-control study in a Mexican population. Auton Neurosci. 2014; 183:66-71. DOI: 10.1016/j.autneu.2014.01.005. View

13.

Colman N, Nahm K, Ganzeboom K, Shen W, Reitsma J, Linzer M . Epidemiology of reflex syncope. Clin Auton Res. 2004; 14 Suppl 1:9-17. DOI: 10.1007/s10286-004-1003-3. View

14.

Newton J, Kenny R, Lawson J, Frearson R, Donaldson P . Prevalence of family history in vasovagal syncope and haemodynamic response to head up tilt in first degree relatives: preliminary data for the Newcastle cohort. Clin Auton Res. 2003; 13(1):22-6. DOI: 10.1007/s10286-003-0077-7. View

15.

Klein K, Bromhead C, Smith K, OCallaghan C, Corcoran S, Heron S . Autosomal dominant vasovagal syncope: clinical features and linkage to chromosome 15q26. Neurology. 2013; 80(16):1485-93. DOI: 10.1212/WNL.0b013e31828cfad0. View

16.

Demir E, Hasdemir C, Ak H, Atay S, Aydin H . Genome-Wide Association Study of Copy Number Variations in Patients with Familial Neurocardiogenic Syncope. Biochem Genet. 2016; 54(4):487-494. DOI: 10.1007/s10528-016-9735-z. View

17.

Mathias C, Deguchi K, Schatz I . Observations on recurrent syncope and presyncope in 641 patients. Lancet. 2001; 357(9253):348-53. DOI: 10.1016/S0140-6736(00)03642-4. View

18.

Stewart J, Medow M, Sutton R, Visintainer P, Jardine D, Wieling W . Mechanisms of Vasovagal Syncope in the Young: Reduced Systemic Vascular Resistance Versus Reduced Cardiac Output. J Am Heart Assoc. 2017; 6(1). PMC: 5523632. DOI: 10.1161/JAHA.116.004417. View

19.

Zelazowska M, Lelonek M, Fendler W, Pietrucha T . Arg389Gly β1-adrenergic receptor polymorphism and susceptibility to syncope during tilt test. Arch Med Sci. 2014; 10(2):240-5. PMC: 4042044. DOI: 10.5114/aoms.2014.42576. View

20.

Albert P, Le Francois B, Millar A . Transcriptional dysregulation of 5-HT1A autoreceptors in mental illness. Mol Brain. 2011; 4:21. PMC: 3130656. DOI: 10.1186/1756-6606-4-21. View