Endothelin system polymorphisms in tilt test-induced vasovagal syncope

Abstract

Genetics may be involved in the pathophysiology of vasovagal syncope. The 3A/4A polymorphism of the EDN1 gene affects the expression of endothelin-1, and the H323H T/C polymorphism of the EDNRA gene encoding for the endothelin type A receptor has been associated with cardiovascular pathologies. As the endothelin system participates in the regulation of cardiovascular homeostasis, the aim of this study was to analyse the role of these genetic variants in influencing tilt-induced vasovagal syncope. We recorded the cardiovascular parameters of 107 otherwise healthy subjects with recurrent unexplained syncope who underwent a head-up tilt test; 58 (54%) fainted. In terms of the EDNRA polymorphism, eight subjects (8%) had the T/T genotype, 41 were heterozygous (38%) and 58 homozygous (54%) for the C allele. Sixty subjects (56%) carried homozygosis for the 3A allele of the EDN1 polymorphism and 47 were heterozygous (44%). The 4A allele was significantly more frequent in the patients who responded positively to the tilt test than in those who did not: the relative odds ratios and confidence intervals at univariate and multivariate analyses were respectively 2.37 (1.07-5.26) and 2.41 (1.05-5.49). Comparisons with a control group further supported these data. Among the tilt-positive patients, the carriers of the 4A allele were more likely to have a vasodepressive pattern than those who were homozygous for the 3A variant. In conclusion, the 3A/4A polymorphism of the EDN1 gene affects susceptibility to syncope, and the 4A variant associated with increased endothhelin-1 expression may promote vasodepressive hemodynamic responses during tilt testing.