A polymorphism in the endothelin-A receptor gene is linked to baroreflex sensitivity.
BACKGROUND
The baroreflex plays an essential role in regulating the cardiovascular system. However, very few studies have focused on the links between genetic polymorphisms and baroreflex sensitivity (BRS).


METHODS
A total of 146 hypertensive individuals who had never been treated, and 105 healthy individuals (controls) were included in the study. The genotypes of 17 polymorphisms of 11 genes involved in the regulation of the cardiovascular system were studied. BRS was measured using a sequence method: BRS was evaluated as the slope of spontaneous increases [systolic blood pressure (SBP)+/reflex response (RR)+] or decreases (SBP-/RR-) in SBP and pulse interval by recording blood pressure (BP) continuously for 20 min.


RESULTS
Following univariate analysis, the genetic polymorphism of endothelin receptor A EDNRA/C+1222T was found to be significantly correlated with the BRS (SBP-/RR-) level in both populations. In normotensive subjects, mean BRS values (SBP-/RR-) were 11.93 +/- 3.69 ms/mmHg in EDNRA CC homozygotes, 9.94 +/- 2.97 ms/mmHg in CT heterozygotes and 9.51 +/- 3.16 ms/mmHg in TT homozygotes (P = 0.01). In hypertensive subjects, mean BRS values (SBP-/RR-) were 9.26 +/- 3.59 ms/mmHg in EDNRA CC homozygotes, 9.03 +/- 4.14 ms/mmHg in CT heterozygotes and 6.60 +/- 2.42 ms/mmHg in TT homozygotes (P = 0.01). After adjustment for age, sex, SBP and diastolic blood pressure and body mass index, the EDNRA/C+1222T polymorphism remained significantly correlated with BRS in both normotensive (P = 0.01) and hypertensive (P = 0.01) subjects.


CONCLUSIONS
These results suggest that the endothelin system may be involved in the regulation of BRS in humans. In particular, the T allele of the EDNRA/C+1222T polymorphism is associated with a reduction in BRS in both healthy and hypertensive subjects.
Ormezzano
Olivier
O
Service de Cardiologie et Hypertension Artérielle, Grenoble, France. oormezzano@chu-grenoble.fr
Poirier
Odette
O
Mallion
Jean-Michel
JM
Nicaud
Viviane
V
Amar
Jacques
J
Chamontin
Bernard
B
Mounier-Véhier
Claire
C
François
Patrice
P
Cambien
François
F
Baguet
Jean Philippe
JP
D000328:Adult; D000483:Alleles; D000704:Analysis of Variance; D017704:Baroreflex / Q000235:genetics*; D001794:Blood Pressure / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D044022:Receptor, Endothelin A / Q000235:genetics*; D012044:Regression Analysis
D044022:Receptor, Endothelin A