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 A 1166C) 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 A 1166C 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 A 1166C 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 genotypes 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 1 allele is weakly associated with increased stiffness.
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 (AGTR1A 1166C) 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 AGTR1A 1166C 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 AGTR1A 1166C 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 genotypes 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 1 allele is weakly associated with increased stiffness.
Authors: Gary F Mitchell; Germaine C Verwoert; Kirill V Tarasov; Aaron Isaacs; Albert V Smith; Ernst R Rietzschel; Toshiko Tanaka; Yongmei Liu; Afshin Parsa; Samer S Najjar; Kevin M O'Shaughnessy; Sigurdur Sigurdsson; Marc L De Buyzere; Martin G Larson; Mark P S Sie; Jeanette S Andrews; Wendy S Post; Francesco U S Mattace-Raso; Carmel M McEniery; Gudny Eiriksdottir; Patrick Segers; Ramachandran S Vasan; Marie Josee E van Rijn; Timothy D Howard; Patrick F McArdle; Abbas Dehghan; Elizabeth S Jewell; Stephen J Newhouse; Sofie Bekaert; Naomi M Hamburg; Anne B Newman; Albert Hofman; Angelo Scuteri; Dirk De Bacquer; Mohammad Arfan Ikram; Bruce M Psaty; Christian Fuchsberger; Matthias Olden; Louise V Wain; Paul Elliott; Nicholas L Smith; Janine F Felix; Jeanette Erdmann; Joseph A Vita; Kim Sutton-Tyrrell; Eric J G Sijbrands; Serena Sanna; Lenore J Launer; Tim De Meyer; Andrew D Johnson; Anna F C Schut; David M Herrington; Fernando Rivadeneira; Manuela Uda; Ian B Wilkinson; Thor Aspelund; Thierry C Gillebert; Luc Van Bortel; Emelia J Benjamin; Ben A Oostra; Jingzhong Ding; Quince Gibson; André G Uitterlinden; Gonçalo R Abecasis; John R Cockcroft; Vilmundur Gudnason; Guy G De Backer; Luigi Ferrucci; Tamara B Harris; Alan R Shuldiner; Cornelia M van Duijn; Daniel Levy; Edward G Lakatta; Jacqueline C M Witteman Journal: Circ Cardiovasc Genet Date: 2011-11-08
Authors: Eliecer Coto; María Palacín; María Martín; Mónica G Castro; Julián R Reguero; Cristina García; José R Berrazueta; César Morís; Blanca Morales; Francisco Ortega; Ana I Corao; Marta Díaz; Beatriz Tavira; Victoria Alvarez Journal: J Transl Med Date: 2010-07-01 Impact factor: 5.531