(Circulation. 1996;94:698-703.)
© 1996 American Heart Association, Inc.
Articles |
Influence of Angiotensin-Converting Enzyme and Angiotensin II Type 1 Receptor Gene Polymorphisms on Aortic Stiffness in Normotensive and Hypertensive Patients
INSERM U337, Broussais Hospital (A.B., S.G., J.T., R.A., M.S.); INSERM SC7 (S.R., O.P., F.C.); INSERM U36, College de France (F.S.); and IPC (L.G., E.L.), Paris, France.
Correspondence to Athanase Benetos, MD, Hopital Broussais (Serv Medecine 1), 96 Rue Didot, 75014 Paris, France.
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 (AGTR1 A1166C) 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 ACE D alleles, but this association became significant only after adjustment for blood pressure (P<.05). Conversely, the AGTR1 A1166C polymorphism was independently associated with aortic stiffness. Mean values of PWV were 11.6±2.7 m/s in AGTR1 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 AGTR1 A1166C 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 AGTR1 and ACE geno-types are involved in the regulation of aortic rigidity. The presence of the AGTR1 C allele is a strong independent determinant of aortic stiffness, whereas presence of the ACE I allele is weakly associated with increased stiffness.
Key Words: angiotensin • aorta • genetics • hypertension
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