Synergistic effect of angiotensin II type 1 receptor and endothelial nitric oxide synthase gene polymorphisms on...

Angiotensin II and nitric oxide belong to important factors in the functional and structural changes of vessel wall, leading to its increased stiffness. We investigated, whether common mutations of angiotensin II type 1 receptor (AGTR(1)) and endothelial nitric oxide synthase (eNOS) are associated with increased arterial stiffness. Two polymorphisms, A(1166)C of AGTR(1) and T(786)C of Enos, were estimated in a random, general population-based sample of 250 subjects. Arterial stiffness was measured using Sphygmocor as aortic (carotid-femoral) and peripheral (femoral-tibial) pulse wave velocities (PWV). Carriers of 3-4 mutant alleles from both polymorphisms, that is, homozygous for both mutations or homozygous for one and heterozygous for the second one, showed significantly higher peripheral PWV (17.92+/-2.40) than those with none or only 1-2 mutant alleles (12.37+/-0.51; P<0.003). Carriers of 3-4 mutant alleles had three times higher risk of having increased peripheral PWV (>or= 13.63 m s(-1), that is, in the top quartile) and this association remained significant after adjustment for potential confounders. No association was found between estimated genotypes and aortic PWV. In conclusion, combination of A(1166)C of AGTR(1) and T(786)C of eNOS mutations increased stiffness of muscular-type arteries.