Influence of angiotensin-converting enzyme and angiotensin II type 1 receptor gene polymorphisms on aortic stiffness in normotensive and hypertensive patients

Background Clinical and experimental studies have demonstrated a major role of the renin-angiotensin system in the functional and structural changes of the large arteries in hypertension. Because genetic studies may help us to understand the mechanisms underlying the involvement of this system in arterial regulation, the present study was designed to assess the contribution of polymorphisms of the ACE insertion/deletion (I/D) and angiotensin II type 1 receptor (AGTR(1)A(1166)C) genes on aortic stiffness regulation. Methods and Results This study included 311 untreated hypertensive and 128 normotensive subjects. Aortic stiffness was evaluated by measurement of the carotid-femoral pulse-wave velocity (PWV). In normotensive subjects, the two polymorphisms did not influence any of the studied parameters. In hypertensive subjects, there was a decreasing trend of mean PWV with the number of ACED alleles, but this association became significant only after adjustment for blood pressure (P <.05). Conversely, the AGTR(1) A(1166)C polymorphism was independently associated with aortic stiffness. Mean values of PWV were 11.6+/-2.7 m/s in AGTR(1) AA homozygotes, 13.3+/-3.3 m/s. in AC heterozygotes, and 15.3+/-4.3 m/s in CC homozygotes (P <.0001 and P <.00001 after adjustment for age and mean blood pressure, respectively). The percentage of variance of PWV explained by AGTR(1) A(1166)C polymorphism (11.6%) was much larger than that of ACE I/D polymorphism (1.7%). Conclusions These results suggest that in hypertensive but not normotensive subjects, the AGTR(1) and ACE genotypes are involved in the regulation of aortic rigidity. The presence of the AGTR(1) C allele is a strong independent determinant of aortic stiffness, whereas presence of the ACE I allele is weakly associated with increased stiffness.