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

Objectives Arterial stiffness is associated with excess morbidity and mortality, independently of other cardiovascular risk factors. Age is the main determinant responsible for arterial wall changes leading to arterial stiffening. 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 relationship between age and aortic stiffness was influenced by genetic variants of angiotensinogen (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 aldosterone synthase (CYP11B(2) T-344/C). This study was realized in 441 untreated hypertensive subjects of European origin (aged 18-74 years). Aortic stiffness was assessed by carotid-femoral pulse wave velocity (PWV), Results Carriers of the angiotensin II type 1 receptor (-153)G allele showed a steeper age/PWV relationship than the AT(1) (-153)AA subjects. The effect 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 relationship age/PWV is shifted upward, indicating higher values of aortic stiffness 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 these 2 genotypes on aortic stiffness, Angiotensinogen, ACE and CYP11 B-2 genotypes did not influence the effects of age on PWV, Conclusions AT(1) receptor genotypes could influence arterial ageing in hypertensive subjects. These results also show that the association between genotypes and arterial stiffness may manifest itself later in life. J Hypertens 19:407-413 (C) 2001 Lippincott Williams & Wilkins.