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Journal of Translational Medicine

, 6:11

First Online: 10 March 2008Received: 18 October 2007Accepted: 10 March 2008DOI: 10.1186-1479-5876-6-11

Cite this article as: Pacanowski, M.A., Zineh, I., Li, H. et al. J Transl Med 2008 6: 11. doi:10.1186-1479-5876-6-11

Abstract

BackgroundAdrenergic gene polymorphisms are associated with cardiovascular and metabolic phenotypes. We investigated the influence of adrenergic gene polymorphisms on cardiovascular risk in women with suspected myocardial ischemia.

MethodsWe genotyped 628 women referred for coronary angiography for eight polymorphisms in the α1A-, β1-, β2- and β3-adrenergic receptors ADRA1A, ADRB1, ADRB2, ADRB3, respectively, and their signaling proteins, G-protein β 3 subunit GNB3 and G-protein α subunit GNAS. We compared the incidence of death, myocardial infarction, stroke, or heart failure between genotype groups in all women and women without obstructive coronary stenoses.

ResultsAfter a median of 5.8 years of follow-up, 115 women had an event. Patients with the ADRB1 Gly389 polymorphism were at higher risk for the composite outcome due to higher rates of myocardial infarction adjusted hazard ratio HR 3.63, 95% confidence interval 95%CI 1.17–11.28; Gly-Gly vs. Arg-Arg HR 4.14, 95%CI 0.88–19.6. The risk associated with ADRB1 Gly389 was limited to those without obstructive CAD n = 400, Pinteraction = 0.03, albeit marginally significant in this subset HR 1.71, 95%CI 0.91–3.19. Additionally, women without obstructive CAD carrying the ADRB3 Arg64 variant were at higher risk for the composite endpoint HR 2.10, 95%CI 1.05–4.24 due to subtle increases in risk for all of the individual endpoints. No genetic associations were present in women with obstructive CAD.

ConclusionIn this exploratory analysis, common coding polymorphisms in the β1- and β3-adrenergic receptors increased cardiovascular risk in women referred for diagnostic angiography, and could improve risk assessment, particularly for women without evidence of obstructive CAD.

Trial RegistrationClinicalTrials.gov NCT00000554.

Electronic supplementary materialThe online version of this article doi:10.1186-1479-5876-6-11 contains supplementary material, which is available to authorized users.

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Autor: Michael A Pacanowski - Issam Zineh - Haihong Li - B Delia Johnson - Rhonda M Cooper-DeHoff - Vera Bittner - Dennis M Mc

Fuente: https://link.springer.com/







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