Key result
The α2B-AR Glu12/12 genotype was associated with consistently elevated adenylate cyclase activity and a lower incidence of syncope during head-up tilt testing compared to the Glu9/12 heterotype in patients with neurally mediated syncope.
Why the study?
Neurally mediated syncope arises from a neural reflex with an unknown underlying cause, and fluctuations in adenylate cyclase activity linked to signal transduction variations were hypothesized to contribute.
Does the α2B-AR gene polymorphism (Glu12 vs Glu9) affect adenylate cyclase activity and the frequency of vasodepressor-type neurally mediated syncope during a head-up tilt test?
Case-Control (n=70)
No
Does the α2B-AR gene polymorphism (Glu12 vs Glu9) affect adenylate cyclase activity and the frequency of vasodepressor-type neurally mediated syncope during a head-up tilt test?
Absolute Event Rate: 0.66% vs 0.56%
p-value: p=0.006
Patients with the Glu12/12 homotype of the α2B-AR gene exhibit elevated adenylate cyclase activity, which may help maintain blood pressure and prevent neurally mediated syncope during prolonged standing compared to those with the Glu9/12 heterotype.
May aid syncope risk stratification; hypothesis-generating and requires prospective validation before clinical use.
Neurally mediated syncope (NMS) arises from a neural reflex; however, its underlying cause remains unknown. Previous research has shown that variations in the Gi-α signal transduction rate led to changes in adenylate cyclase (AC) activity levels. Thus, we hypothesized that these fluctuations in AC activity could contribute to NMS. This study aimed to investigate the receptor genes associated with glutamate (Glu) repeat polymorphism sites Glu12 and Glu9 in the α2B-AR gene. A total of 50 patients with vasodepressor-type (VT)-NMS and 20 healthy volunteers were included in this study. We assessed AC activity levels and blood pressure responses during the head-up tilt (HUT) test and conducted a Glu repeat polymorphism analysis to explore its potential association with NMS. Our findings showed significantly higher AC activity in patients with the Glu12/12 homotype than healthy volunteers across all four HUT test points. Conversely, patients with the Glu9/12 heterotype exhibited a significant difference only 10 min after the test initiation, suggesting a pronounced activation effect of the β2-AR Gs-α subunit in these individuals. Both genotypes displayed the greatest blood pressure fluctuations under 70° tilt stress, with patients with Glu12/12 showing consistent cardiac load and higher values than those with Glu9/12 at two points. Notably, the frequency of NMS onset within 20 min during the tilt test varied, with one Glu12/12 patient and seven Glu9/12 patients experiencing syncope. Additionally, patients with the Glu9/12 heterotype were found to have a higher risk of syncope after prolonged standing compared to those with the Glu12/12 homotype. These results suggest that patients with the Glu12/12 homotype exhibit elevated AC activity levels, which may help increase blood pressure to prevent syncope. This study underscores that variations in AC activity among different gene types could influence the frequency of NMS onset during standing.
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Komiyama et al. (2025) conducted a case-control in Vasodepressor-type neurally mediated syncope (n=70). α2B-AR gene polymorphisms (Glu12/12 and Glu9/12) vs. Healthy volunteers and alternate genotypes was evaluated on Adenylate cyclase activity at baseline (VT-NMS vs healthy volunteers) (p=0.006). The α2B-AR Glu12/12 genotype was associated with consistently elevated adenylate cyclase activity and a lower incidence of syncope during head-up tilt testing compared to the Glu9/12 heterotype in patients with neurally mediated syncope.
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