Endothelin gene variants and aortic and cardiac structure in never-treated hypertensives.
BACKGROUND
The polymorphism of several candidate genes has been studied in relation to essential hypertension and cardiovascular complications. Target organ damage in essential hypertension is a complex disorder influenced by multiple genetic and environmental factors. The possible contribution of endothelin gene variants to target organ damage in hypertension in humans has not been studied in depth.


METHODS
We assessed the influence of genetic variants of components of the endothelin system ETAR -231A/G, 1363C/T, ETBR 30G/A and endothelin-1 (ET-1) 138insertion/deletion (I/D) on aortic stiffness, left ventricular geometric, and radial artery parameters in 528 never-treated hypertensive subjects of European origin. The study population included 314 men and 214 women with a mean age of 48+/-0.5 years (+/-SEM). In samples of patients, aortic stiffness was assessed with carotid-femoral pulse wave velocity (PWV). Radial artery thickness was measured with an echotracking angiometer and left ventricular geometric parameter with standard echographic procedures.


RESULTS
The main results showed that the ETAR-231A/G (P = .022) and the ETBR 30G/A (P = .026) receptor gene variants influenced PWV level in women. The -231G and 30G alleles were associated with a codominant increase in PWV, explaining 18.6% of its variability (P = .005). In men, the ETBR 30G/A receptor gene variant was also related to the level of radial artery parameters (P = .02). No association between the 138I/D polymorphism of the ET-1 gene and left ventricular and radial artery parameters was observed in either men or women.


CONCLUSIONS
These results indicate that the influence of endothelin system genes can be detected first on arterial parameters.
Lajemi
M
M
Unité INSERM U337, Institut des Cordeliers, Paris, France.
Gautier
S
S
Poirier
O
O
Baguet
J P
JP
Mimran
A
A
Gosse
P
P
Hanon
O
O
Labat
C
C
Cambien
F
F
Benetos
A
A
D000328:Adult; D000368:Aged; D001011:Aorta / Q000502:physiology*; D006332:Cardiomegaly / Q000000981:diagnostic imaging; D004452:Echocardiography; D019332:Endothelin-1 / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011673:Pulsatile Flow / Q000502:physiology*; D017534:Radial Artery / Q000502:physiology; D017466:Receptors, Endothelin / Q000235:genetics*
D019332:Endothelin-1; D017466:Receptors, Endothelin