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.
Highlights
There are several reasons to suspect a genetic origin of vasovagal syncope
The alpha adrenergic 1 receptor ADRA1A 1039T>C variant is involved in sympathetic transduction, and the Arg/Arg genotype of ADRA1A 1039 T>C significantly associated with positive tilt tests when comparing vasovagal syncope patients to asymptomatic controls with negative tilt tests [29]
We found no evidence that this allele associates with vasovagal syncope subjects compared to unaffected family members [18]
Summary
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. The control subjects are usually those who faint, but have negative tilt tests, making the conclusions about association with the clinical phenotype less certain. A recent large, candidate gene study of kindreds with high, multigenerational prevalence of the vasovagal syncope identified 3 genes that associate with vasovagal syncope.
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