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.Procedure: 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 ven-tricular 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.