Endothelin system polymorphisms in tilt test-induced vasovagal syncope.
OBJECTIVE
As the endothelin system participates in the regulation of cardiovascular homeostasis, the aim of this study was to analyse the role of endothelin system polymorphisms in influencing tilt-induced vasovagal syncope.


METHODS
We evaluated 107 otherwise healthy subjects with recurrent unexplained syncope who underwent a head-up tilt test. All subjects were genotyped for the 3A/4A polymorphism of the EDN1 gene and the H323H T/C polymorphism of the EDNRA gene.


RESULTS
Fifty-eight patients (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.


CONCLUSIONS
The 3A/4A polymorphism of the EDN1 gene affects susceptibility to syncope, and the 4A variant associated with increased endothelin-1 expression may promote vasodepressive hemodynamic responses during tilt testing.
Sorrentino
Sandro
S
Cardiology Unit, Emergency and Organ Transplantation Dept., University of Bari, Piazza Giulio Cesare 11, 70124, Bari, Italy.
Forleo
Cinzia
C
Iacoviello
Massimo
M
Guida
Pietro
P
D'Andria
Valentina
V
Favale
Stefano
S
D000328:Adult; D000483:Alleles; D016232:Endothelins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D019462:Syncope, Vasovagal / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*; D018667:Tilt-Table Test
D016232:Endothelins