Angiotensin II type 1 receptor (-153)A/G and (1166)A/C gene polymorphisms and increase in aortic stiffness with age in hypertensive subjects

Objectives Arterial stiffness is associated with excess morbidity and morta lity, independently of other cardiovascular risk factors. Age is the main d eterminant responsible for arterial wall changes leading to arterial stiffe ning. Environmental and genetic factors may however influence the magnitude of the effects of age on large artery stiffness, Design and methods The present study assessed whether or not the relationsh ip between age and aortic stiffness was influenced by genetic variants of a ngiotensinogen (AGT T-174/M, M-235/T), angiotensin converting enzyme (ACE I /D), angiotensin II type 1 receptor(AT(1) (1166)A/C, (-153)A/G) and aldoste rone synthase (CYP11B(2) T-344/C). This study was realized in 441 untreated hypertensive subjects of European origin (aged 18-74 years). Aortic stiffn ess was assessed by carotid-femoral pulse wave velocity (PWV), Results Carriers of the angiotensin II type 1 receptor (-153)G allele showe d a steeper age/PWV relationship than the AT(1) (-153)AA subjects. The effe ct of the AT(1) (-153)A/G polymorphism on aortic stiffness became apparent after the age of 55 years, In subjects with the AT(1) C-1166 allele, the re lationship age/PWV is shifted upward, indicating higher values of aortic st iffness at any age compared to the A(1) (1166)AA patients, Carriers of both the AT(1) C-1166 and (-153)G alleles presented the additive effects of the se 2 genotypes on aortic stiffness, Angiotensinogen, ACE and CYP11 B-2 geno types did not influence the effects of age on PWV, Conclusions AT(1) receptor genotypes could influence arterial ageing in hyp ertensive subjects. These results also show that the association between ge notypes and arterial stiffness may manifest itself later in life. J Hyperte ns 19:407-413 (C) 2001 Lippincott Williams & Wilkins.