Genetic aspects of vasovagal syncope: a systematic review of current evidence
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Europace (2009) 11, 414–420 REVIEW
doi:10.1093/europace/eun387
Genetic aspects of vasovagal syncope: a
systematic review of current evidence
Louise R.A. Olde Nordkamp 1, Wouter Wieling 1, Aeilko H. Zwinderman 2,
Arthur A.M. Wilde 3, and Nynke van Dijk 2*
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1
Department of Internal Medicine, Academic Medical Centre, Amsterdam, The Netherlands; 2Department of Clinical Epidemiology Biostatistics and Bioinformatics,
Academic Medical Centre, PO Box 22700, 1100 DE Amsterdam, The Netherlands; and 3Department of Cardiology, Academic Medical Centre, Amsterdam,
The Netherlands
Received 2 September 2008; accepted after revision 22 December 2008; online publish-ahead-of-print 18 January 2009
Knowledge on the aetiology of vasovagal syncope (VVS) is of great importance to optimize its diagnostic and therapeutic options. To unravel
the largely unknown pathophysiology, studies on genetic aspects of VVS can be of use. This systematic review on all available literature aims
to provide an overview of the current knowledge of VVS genetics. The MEDLINE and EMBASE database were systematically searched for all
studies discussing genetic factors as a cause of VVS. Hereditary aspects of VVS were studied in 19 studies. Six studies determined a positive
family history in, respectively, 19 –90% of the VVS patients. These numbers, however, are not higher than the cumulative incidence of VVS in
the general population (35–39%). Four studies examined potential genetic polymorphisms associated with VVS. Only a Gly389 allele was
more frequently present in VVS patients with a positive HUT test, although the significance level was set much higher than usual in
genetic studies, and this result has not been replicated so far. Knowledge on genetic aspects of VVS could be very useful in clinical practice
and research, but the current evidence that it has a genetic basis is not very strong.
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Keywords Syncope † Vasovagal syncope † Genetics † Family history † Twins
review the available literature on VVS genetics and provide an over-
Introduction view of current knowledge.
Vasovagal syncope (VVS) is transient loss of consciousness due to a
sudden drop of blood pressure (BP) caused by reflex peripheral
vasodilatation combined with bradycardia.1 Vasovagal syncope is Methods
a common condition in the general population. The lifetime
cumulative incidence in subjects up to 65 years is 35– 39%.2,3 Search strategies and extraction
Vasovagal syncope reduces the quality of life of patients significantly, of relevant results
particularly in patients with recurrent episodes.4,5 Mortality rate We searched the MEDLINE database (Pubmed; 1950 to 19 November
for VVS is almost zero,6 but it can be misinterpreted for 2007) and the EMBASE database (Ovid; 1988 to 19 November 2007),
more dangerous conditions, like cardiac syncope,6 and result in danger- using the search terms described in Table 1. We also searched on 3
ous situations, like when driving.7 To optimize the diagnostic and December 2007 the Dutch Trial Register (www.trialregister.nl), the
therapeutic options for VVS, knowledge of its aetiology is important. trial register of the National Institute of Health (www.clinicaltrials.gov),
To unravel the largely unknown pathophysiology,8 studies on the and the metaRegister of Controlled Trials (www.controlled-trials.com),
genetic basis of VVS could be useful. These studies could also be of using the search term ‘syncope’ for ongoing studies on this subject.
importance for developing new diagnostic methods,9,10 overcoming
classification difficulties by more accurate classification of syncope, Criteria for inclusion of studies
finding new therapy targets, and predicting therapy responses. For this systematic review, we considered all studies discussing genetic
Determining the role of genetic factors might also lead to a better factors as a cause of VVS. Vasovagal syncope was defined as transient
understanding of the influence of environmental factors in VVS10 loss of consciousness due to reflex vasodilatation and/or bradycardia,
and why VVS is more frequent in women than in men2,11 and in resulting in a sudden drop in BP. It can be provoked by stressors
white people than in black people.12 In this study, we systematically such as strong emotions or prolonged standing. The diagnosis of
* Corresponding author. Tel: þ31 20 5668975, Fax: þ31 20 6912683, Email: n.vandijk@amc.uva.nl
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org.Genetic aspects of VVS 415
Table 1 Search terms used for the MEDLINE and EMBASE database
MEDLINE (Pubmed): 1950 to 19 November 2007
..............................................................................................................................................................................
((‘Genetics’[Mesh]) OR (‘Histocompatibility Testing’[Mesh]) OR (‘Genetic Processes’[Mesh]) OR (‘Genetic Phenomena’[Mesh]) OR (‘Genetic
Structures’[Mesh]) OR (‘genetics’[Subheading]) OR (‘Heredity’[Mesh]) OR (heredit*) OR (‘Siblings’[Mesh] OR ‘Twin Studies’[Mesh]) OR
(‘Family’[Mesh]) OR (‘Pedigree’[Mesh]) OR (Genealogic Tree*) OR (Family Tree*) OR ((‘Twins’[Mesh] OR ‘Twin Studies’[Mesh] OR ‘Twin Study
‘[Publication Type]) OR (‘Multiple Birth Offspring’[Mesh] OR ‘Genetics, Medical’[Mesh])))
AND
((((‘syncope’[MeSH Terms] OR syncope[Text Word]) OR (syncope*) OR (vasovagal syncope*) OR (faint*) OR (Syncopal Episode*) OR (Syncopal
Vertigo) OR (Cardiogenic Syncope*) OR (Carotid Sinus Syncope*) OR (Effort Syncope*) OR (Situational Syncope*) OR (Tussive Syncope*) OR
(neurally mediated syncope) OR (postural syncope*) OR (Micturition Syncope*) OR (Drop Attack*))) OR ((collapse*)))
AND
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((Humans[Mesh]) AND (English[lang] OR Dutch[lang]))
EMBASE (OVID): 1988 to 19 November 2007
..............................................................................................................................................................................
(exp genetics/) OR (histocompatibility test/) OR (exp heredity/) OR (genetic variability/) OR (heredit$.mp. [mp¼title, abstract, subject headings, heading
word, drug trade name, original title, device manufacturer, drug manufacturer name]) OR (Siblings.mp. [mp¼title, abstract, subject headings, heading
word, drug trade name, original title, device manufacturer, drug manufacturer name]) OR (siblings$.mp.) OR (exp Twins/) OR (twin studies.mp.) OR (exp
family/) OR (exp genetic analysis/ or pedigree analysis/) OR (Genealogic Tree$.mp.) OR (Family Tree$.mp. [mp¼title, abstract, subject headings, heading
word, drug trade name, original title, device manufacturer, drug manufacturer name]) OR (exp Multiple Pregnancy/) OR (exp medical genetics/)
AND
(exp unconsciousness/) OR (syncope$.mp. [mp ¼ title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug
manufacturer name]) OR (SYNCOPE/ or HEAT SYNCOPE/) OR (vasovagal syncope$.mp.) OR (faint$.mp. [mp ¼ title, abstract, subject headings,
heading word, drug trade name, original title, device manufacturer, drug manufacturer name]) OR (Syncopal Episode$.mp. [mp ¼ title, abstract, subject
headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]) OR (Cardiogenic Syncope.mp.) OR (carotid
sinus syncope/ or Carotid Sinus Syncope.mp.) OR (Effort Syncope.mp.) OR (Situational Syncope.mp.) OR (Tussive Syncope.mp.) OR (neurally
mediated syncope.mp.) OR (postural syncope.mp.) OR (micturition syncope/ or Micturition Syncope.mp.) OR (Drop Attack.mp. or Drop Attack/) OR
(collapse$.mp. [mp ¼ title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name])
AND
Limit to (human AND (dutch OR english))
VVS is made based on typical history, head-up tilt (HUT) testing, or a larger amount of evidence provide more statistical power for a pre-
combination of both.1 sumed association. The second pillar is the extent of replication,
We considered all types of studies, involving human participants which counteracts inconsistencies between studies such as statistical
of any age group and of either sex. All study designs and various considerations and also epidemiological considerations for the stan-
outcomes were considered. They included: studies with descriptive dardization or at least harmonization of phenotyping, genotyping and
information on families with VVS; studies with quantitative measures analytical models across studies. The third pillar is the protection
of the number of relatives with VVS in fainting and non-fainting from biases, which contains a consideration of biases in phenotype
subjects; familial studies with haemodynamic measures during stress; definition, biases in genotyping, population stratification, and, for
studies determining the prevalence of specific genetic polymorphisms meta-analysis only, selective reporting biases.
in subjects with and without VVS; and studies calculating the impact Two authors (L.R.A.O.N. and N.D.) assessed all included association
of genetic polymorphisms on VVS. studies independently on the three pillars. Thereafter, they labelled
Two authors (L.R.A.O.N. and N.D.) independently reviewed the studies as ‘strong’, ‘moderate’, or ‘weak’ epidemiological credibility.
titles of the retrieved studies for eligibility. Studies with titles describing Disagreements on the study’s credibility were resolved by discussion
unrelated diseases, sudden death of participants, non-human partici- or, where necessary, by a third person (A.H.Z.).
pants, or in vitro research were excluded. Disagreements between
the two authors regarding a study’s eligibility were resolved by discus- Data extraction
sion or, where necessary, by a third person (W.W.).
Two authors (L.R.A.O.N. and N.D.) examined the results of the
Of the eligible studies the abstracts, or if necessary, the paper was
included studies and extracted the results for this review indepen-
read. A study was included if human participants with VVS were
dently. Disagreements between the authors regarding the results
studied and if the topic was familial VVS or genetics of VVS.
were resolved by discussion resulting in consensus or, where necess-
Secondly, the search was extended by searching the references
ary, a third person (W.W.).
of the obtained papers for relevant studies that fitted the inclusion
criteria. Only articles written in English and Dutch were used.
Methodological quality Results
The quality/credibility of genetic association studies was assessed
using the guidelines of Ioannidis et al.13 In these guidelines, a semi- Selection of studies
quantitative index is calculated on the basis of three pillars. The first The MEDLINE and the EMBASE search yielded 2021 and 2109
pillar is the amount of evidence, which ensures that studies with a results, respectively. None of the studies in the trial registers416
Table 2 Overview of the included studies
Report Study design Study population Number of Mean Female Main resulta
participants age (%)
(SD)
.............................................................................................................................................................................................................................................
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Talwar et al.14 Case report 70-year-old female index patient with 1 36-year-old daughter also reported syncope with a transient complete AV block during
recurrent VVS with complete AV a syncopal episode
block during syncopal episode
Cooper et al. 18 Case report 19-year-old female index patient 1 Mother also reported recurrent syncope
reporting recurrent VVS
Mathias et al. 21 Case report 11-year-old female index patient with 1 Paternal grandmother, father, and three of five siblings also reported VVS; none of the
recurrent VVS, started at the age of adopted siblings reported VVS
2.5
Newton et al.24 Case report 10-year-old index patient (unknown 1 Sibling, father, paternal grandfather, brother and sister of paternal grandfather, paternal
gender) with recurrent syncope uncle, and child of paternal uncle also reported syncope or pre-syncope
Marquez Case–series 20-year-old female index patient with 5 Siblings and father of 20-year-old female also reported recurrent syncope; mother of
et al.26 recurrent VVS; two sets of monozygotic twin sisters also reported recurrent syncope
monozygotic twins all report
recurrent VVS
Kleinknecht Case–control Psychology and sociology students 204 n/a 63 66% of blood-injury-related fainting students report at least one parent with a history
and Lenz15 volunteers of blood-injury-related fainting vs. 41% of non-fainting students
Kleinknecht Case–control Psychology and sociology students 103 n/a 76 94% of the essential fainters (¼ non-anxious blood-injury-related fainters) report a
et al.16 volunteers with a history of blood parental history of fainting
injury fainting
Camfield and Case–control Outpatient visitors of paediatric 30 10 73 90% of fainting children report at least one relative with a history of fainting vs. 33% of
Camfield17 neurologist with history of VVS non-fainting best friends
Mathias et al.22 Case–control Patients with recurrent syncope and 641 46 58 Positive family history in 36% of patients with VVS
pre-syncope referred to a specialized
autonomic unit
Lucas et al. 28 Case–control Fatigued Gulf war veterans 49 n/a n/a Fatigued veterans with VVS had equal or less frequent positive family history on VVS
than fatigued veterans without VVS.
Mathias et al. 20 Cohort study Patients with VVS referred to specialized 119 34.4 65 Familial history of syncope in 37% of the VVS patients (positive HUT patients 51 vs.
autonomic unit 28% in negative HUT patients)
Newton et al. 23 Cohort study HUT-positive VVS patients at the third 441 n/a n/a A family history of syncope was found in 19% of the VVS patients
line cardiovascular investigation unit
Serletis et al.27 Cohort study Medical students and their family 290 39 (16) 51 A student with two fainting parents was more likely to faint than the one with no
fainting parents; offspring of either sex whose mother faints were more likely to faint
L.R.A. Olde Nordkamp et al.
than those whose mother does not faint; having a father who faints significantly
increases the risk of VVS in sons, but not in daughters
Newton et al.25 Case–control HUT-positive VVS patients at the third 165 56 (19) 62 The frequency of ACE insertion –deletion polymorphisms is not higher in subjects with
line cardiovascular investigation unit VVS than in the general population. A family history of syncope was found in 23% of
the the VVS patients
Marquez Case–control Patients with unexplained syncope who 50 27.9 58 The Gly389 allele frequency in positive HUT patients was 30 vs. 3% in the negative
et al. 30 underwent a HUT test HUT group (P ¼ 0.012)Genetic aspects of VVS 417
(154 hits) were applicable to our study. Therefore, with the
positive HUT test. Receptor affinity for adenosine and the relative amount mRNA
(receptor synthesis) were similar in both patients with a positive and negative HUT
The frequency of the GNB3 825C allele was higher in patients with a typical vasovagal
Increased expression and up-regulation of A2A adenosine receptors in patients with a
unique environmental plus additive genetic and/or shared environmental variables
were moderately related and became less similar as the level of orthostatic stress
removal of duplicate studies, 3325 titles were screened. Of
Time to pre-syncope during HUT was similar in twin pairs; haemodynamic variables
Non-blood-injury fainting is best explained by a model assuming shared and unique
environmental variables. Blood fainting was best explained by a model assuming
these, 82 were eligible and 19 fulfilled all inclusion criteria and
were included14 – 32 in this review.
An overview of the selected studies is displayed in Table 2. Four
studies were case reports,14,18,21,24 one was a case series,26 five
were cohort studies,19,20,23,27,29 and nine were case –control
studies.15 – 17,22,25,28,30 – 32
history than in those without a typical vasovagal history
Quality of studies
Overall, the epidemiological evidence of the association studies is
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weak. In most studies, the sample size was smaller than 100 sub-
jects. There were demonstrable inconsistencies between the
included studies and a meta-analysis has not been performed yet.
Finally, the phenotype definition was varying across studies, the
populations were often from different descent, and, if appropriate,
genotyping quality was not examined.
Interpretation of results
increased
The studies on familial VVS suggest a genetic component for VVS
test
by describing recurrent syncope in VVS patients and in relatives
with the same symptoms. The frequency of a positive family
history in VVS patients ranged from 1923 to 90%17 in different
studies (Figure 1). Two studies compared the frequency of a
positive family history of VVS patients to non-VVS patients,
79
48
66
50
both demonstrating a significant difference (9017 and 66%15 in
VVS patients vs. 3317 and 41%15 in non-VVS patients). A positive
35.7 (20)
(11.2)
49.6 (3)
27 (7)
family history most often concerned an affected child or
45.2
parent.17,20
Serletis et al.27 calculated the risk on VVS in subjects with syn-
copal parents in 62 medical students and 228 first-degree relatives.
Offspring with two fainting parents were more likely to faint (65%)
68
33
1318
32
than those with no fainting parents (23%), but offspring with one
fainting parent were not significantly more likely (39%) to faint
Twin pairs volunteering to supply blood
Patients with recurrent syncope (more
episodes of pre-syncope/syncope in
than those with no fainting parents. Offspring of either sex
Patients referred to university hospital
for biochemical and DNA analysis
months) with a positive HUT test
whose mother fainted were more likely to faint than those
than two episodes in the last 3
Monozygotic twin pair volunteers
with two or more unexplained
whose mother did not faint. Fainting fathers increased the risk of
syncope only in their sons, not in their daughters.27
VVS, vasovagal syncope; HUT, head-up tilt test; n/a, result not available.
the preceding year
Case–control
Case–control
Cohort study
Cohort study
Relevant results for this review.
Carrega et al. 32
O’Leary et al.29
Lelonek et al.31
Martin19
Page and
Figure 1 Literature overview in proportion of positive fainting
family history in fainting and non-fainting offspring.
a418 L.R.A. Olde Nordkamp et al.
On the contrary, Lucas et al.28 demonstrated that a family 75% (12[1 2 0.37]3 ¼ 0.75). One study28 found no difference
history of fainting was not a risk factor for neurally mediated hypo- between family members of VVS patients compared to persons
tension in chronically fatigued Gulf War veterans. The frequency of without VVS. The study of Serletis et al.27 described that a fainting
a positive family history in women was even higher in the control mother increased the risk of VVS in either sex, whereas a fainting
group than in the VVS patients (41 vs. 12%; P , 0.01). father only increased the risk in sons. This observation is rather
Three studies demonstrate the possible presence of genetic doubtful in terms of causal genetic nature, since VVS more often
mechanisms of VVS. O’Leary et al.29 demonstrated that the occurs in females in the general population.
capacity to deal with orthostatic stress appears to be similar in The number of studies and amount of evidence provided is low,
16 monozygotic twin pairs, but the haemodynamic variables especially the number of genetic association studies is low. Four
were only moderately related, suggesting the mechanism(s) by studies examined potential genetic polymorphisms associated
which the orthostatic tolerance was achieved varied. Kleinknecht with VVS. Only a Gly389 allele was more frequently present in
et al.16 reported that their group of 103 fainters mostly existed VVS patients with a positive HUT test30 (P ¼ 0.012). Although
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of non-blood-injury-injection fainters (fainting not induced by this is a statistically significant result when considering a P-value
blood phobia). Of this group of non-blood-injury-injection fainters, of ,0.05 significant, in genetic studies the significance level is
94% reported a positive parental fainting history, in contrast to usually set much lower and the results have not been replicated
56% of the blood-injury-injection fainters, suggesting different so far,13 resulting in a very low level of evidence. Although
types of fainting. Page and Martin19 took environmental factors genetic influences on the occurrence of VVS episodes seem plaus-
into account next to genetic factors and the type of fainting. ible, nurture effects have not been excluded19 and specific high-risk
They demonstrated that non-blood-injury fainting is best explained polymorphisms have not been identified so far. Differences in
by a model only assuming shared and unique environmental vari- vasovagal responses between subjects16 and different mechanisms
ables. Blood-injury-injection fainting was best explained by a for the development of orthostatic intolerance29 suggest that
model assuming unique environmental plus additive genetic and/ various genetic polymorphisms could be of significance.
or shared environmental variables, suggesting a possible genetic Several other issues hamper successful research on the genetics
factor only for patients with blood-injury-induced fainting and of VVS. Vasovagal syncope is ill-defined, and researchers disagree
not for other forms of VVS. on the reference standard for VVS. Some studies only include
Four studies examined the influence of specific polymorphisms patients with a positive HUT test,18,20,23 – 26,28 – 30 others use
on the risk of VVS. Newton et al.25 examined the influence of score lists27 and interviews15,16 or only history and physical exam-
angiotensin-converting enzyme insertion/deletion polymorphisms, ination17,19 – 23,32,35 to verify their diagnosis. Study populations also
which could lead to altered circulating angiotensin levels. vary in the number of VVS episodes experienced and age. Some
Carrega et al.32 examined whether adenosine A2A receptor studies18,21,22,24,26,30 – 32 only include patients with recurrent synco-
expression, which acts on blood vessel tone and sinoatrial node, pal episodes, whereas other studies15 – 17,19,27 also include patients
is altered in patients with VVS. Lelonek et al.31 studied the fre- who experienced only one episode of VVS. Considering that up to
quency of GNB3 C825T polymorphisms, enhancing vascular reac- 40% of the population experiences one or more syncopal episodes
tivity in HUT-positive patients with and without a typical vasovagal during their lives, and this cumulative incidence rises with age, one
history, and Márquez et al.30 studied the Gly389 allele frequency, could discuss when the phenotype ‘vasovagal patient’ should be
which leads to a lower contractile responsiveness to catechol- considered present. These differences in definitions and study
amines and therefore dysregulates the autonomic nervous populations make it difficult to compare studies and impossible
system. Only the Gly389 allele polymorphism was more frequently when aiming to pool results. Uniform phenotyping is mandatory
present in VVS patients with a positive HUT test than in HUT- for successful genotyping.
negative subjects.30 None of the other studies showed a difference Additionally, it is known that in many patients with VVS, epi-
in the presence of the studied polymorphisms between patients sodes are triggered by specific environmental triggers such as
with VVS and subjects without VVS. fear or orthostasis.36 Differences in vasovagal responses between
patients with different triggers could be an indication of different
pathogenetic pathways involved and thus different genes and
Discussion genetic markers.
This systematic review included all available studies on genetic Another difficulty resulting from the high incidence of VVS is
aspects of VVS, including case reports to provide a complete over- that it can occur next to other diseases or syndromes and could
view of the available evidence. Hereditary aspects of VVS were therefore easily be misdiagnosed and linked with genetic poly-
described in 19 studies. Five case reports described possible famil- morphisms of other diseases or syndromes.37
ial clustering of VVS.14,18,21,24,26 Six other studies15,17,20,22,23,25 Vasovagal syncope is probably multifactorial, because blockade
determined a positive family history in, respectively, 19% to even of individual pathways does not prevent VVS.38,39 It is also unlikely
90% of the VVS patients. These numbers, however, are not that VVS is caused by single causal mutations. Different sets of
higher than the cumulative incidence of VVS in the general genes in combination with environmental triggers can possibly
population (35 –39%).2,3,11,27,33,34 In fact, if a family consists of lower a threshold, which leads to an increased risk to develop a
three family members (e.g. two parents, one sibling) and the vasovagal episode.
prevalence of VVS in the general population is roughly 37%, the There are multiple potential targets for genetic polymorphisms
chance of an episode of VVS in one of the three members is causing increased risk of VVS.40 Alterations in the water and saltGenetic aspects of VVS 419
regulation, such as the renin –angiotensin –aldosterone system, can to what model inherits VVS? (iv) Which genes are involved? (v)
cause a slight hypovolaemia, which possibly lowers the threshold What is the functional effect of the associated mutations? (vi)
for VVS.41 Another target can be a reduced level of creatine What is the significance of the mutation in the population?60
kinase, leading to reduced potential for vasoconstriction to coun- Until now, mostly familial clustering and correlation of VVS is
teract a sudden drop in BP.42 Additionally, other known regulators studied, suggesting, but not proving, a familial clustering or
of peripheral resistance, such as the arginine vasopressin cascade,43 correlation. Since VVS is a very common condition in the
b2-adrenergic receptors, human urotensine-II,44 and nitric mono- general population,2,3,11,27,33,34 the question arises whether this
oxide cascade,45 or regulators of the sympathetic nerve activity, clustering can be explained by the high prevalence and/or environ-
can also be targets in which genetic polymorphisms can lead to mental factors. Clarification on this part using twin-adoption and
a lower threshold for VVS.46 Known regulators of the heart rate, migration research enables evaluating the impact of genotype
such as regulators of the vagus nerve (familial vagotonia is and environmental factors and segregation analysis to determine
described47) or baroreceptors and regulators of the stroke the model of heritage. Alternatively, large families in which VVS
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volume, are additional options.46 seems highly frequent can be used for classical linkage analysis,
One study in this review27 showed that fainting fathers only providing a potential shortcut to causal genes.
increase the risk in sons, not in daughters. On the contrary, VVS
is in general more common in women. These sex differences
are still not fully understood. Perhaps hormonal factors are of Conclusion
influence in triggering VVS.48 The evidence that VVS has a genetic basis is not very strong.
Identification of gene variants that protect people from VVS or Research is hampered by the absence of necessary conditions,
gene variants associated with diseases with a possible common such as a uniform definition of VVS and the high prevalence in
mechanism, such as motion sickness,49 can lead to understanding the general population. However, knowledge on genetic aspects
VVS genetics. Related disorders such as orthostatic intolerance, of VVS seems interesting and many potential future studies are
postural tachycardia syndrome, or hypertension may have the possible.
same genetic basis or reveal a protective mechanism. Therefore,
genetic research in these disorders can lead to potential
targets50 – 55 for VVS research. For example, Ditto et al.35 found Conflict of interest: none declared.
that inexperienced donors without a parental history of hyperten-
sion had a larger tendency to faint than inexperienced donors Funding
with a parental history of hypertension or experienced donors. All authors are employees of the Academic Medical Center. No
Assuming a genetic basis for hypertension, this study suggests external funding was received for this study.
hypertension is protective of VVS and BP regulatory genes could
be oppositely affected in VVS and hypertension. References
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