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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 (AGTR1) and endothelial nitric oxide synthase (eNOS) are associated with increased arterial stiffness. Two polymorphisms, A1166C of AGTR1 and T786C 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 (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 A1166C of AGTR1 and T786C of eNOS mutations increased stiffness of muscular-type arteries.

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Acknowledgements

The present study was founded by Internal Grant Agency of Czech Ministry of Health (grant no. 9333–3) and by Ministry of Education (grant no. 0021620819). We also used several data from post-MONICA study therefore we would like to acknowledge the cooperation of all investigators who participated on this survey.

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Correspondence to O Mayer Jr.

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Mayer, O., Filipovský, J., Pešta, M. et al. Synergistic effect of angiotensin II type 1 receptor and endothelial nitric oxide synthase gene polymorphisms on arterial stiffness. J Hum Hypertens 22, 111–118 (2008). https://doi.org/10.1038/sj.jhh.1002279

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