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

Abstract

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 (17.9272.40) than those with none or only 1-2 mutant alleles (12.3770.51; Po0.003). Carriers of 3-4 mutant alleles had three times higher risk of having increased peripheral PWV (X13.63 m s À1 , 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.

Association between endothelial NO synthase polymorphisms and arterial properties in the general population

“…Absence of association between other two NOS3 genotypes under study and central arterial properties is in line with our previous findings [15,16]. In these studies, the rs1799983 and rs2070744 polymorphisms were related to the stiffness of peripheral muscular arteries but not to aortic PWV.…”

“…In the Framingham study, rs1799983 was related to central pulse pressure and forward wave amplitude in women [14]. Moreover, we have previously shown the interaction between genes for angiotensin II type 1 receptor (AGTR1, A1166C, rs5186) and NOS3 rs2070744 and stiffness of muscular-type arteries [15]. In the same subjects [16], we observed that current smokers had increased stiffness of muscular arteries in carriers of both rs2070744 and rs1799983 mutations.…”

The Relationship Between eNOS (G894T ) Gene Polymorphism and Arterial Stiffness in Patients with Metabolic Syndrome

“…Mayer et al [41] demonstrated in a study that the homozygous and heterozygous status of T786C polymorphism is accompanied by significantly higher values of pulse wave velocity compared to mutation-free subjects; the same results were reported for G894T polymorphism, in smokers. In contrast, in the group of nonsmokers, eNOS gene polymorphisms were not associated with a significantly higher pulse wave velocity.…”

“…Furthermore, in recent studies, eNOS polymorphism has been associated with arterial stiffness [28], evaluated by the measurement of pulse wave velocity [29,30].…”

Pulse pressure: more than 100 years of changes in stroke volume

“…There are different systems able to look at the reflected waves and estimate the tone of the arterial tree, i.e. Pulsecor and SphygmoCor [23][24][25]. The device used by the authors was the SphygmoCor, which enables PP to be measured non-invasively at the radial site.…”