Confirmation of a role for the 389RG beta-1 adrenoceptor polymorphism on exercise capacity in heart failure
| Autor: | A J Sandilands, K M O’Shaughnessy, Morris J. Brown, S Large, Jayan Parameshwar |
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| Rok vydání: | 2005 |
| Předmět: |
Chronotropic
Inotrope Cardiomyopathy Dilated Male medicine.medical_specialty Heart disease Cardiomyopathy Myocardial Ischemia Physical exercise Scientific Letters Internal medicine medicine Humans Heart Failure Analysis of Variance Exercise Tolerance Polymorphism Genetic business.industry Dilated cardiomyopathy Middle Aged medicine.disease Endocrinology Heart failure Circulatory system Female Receptors Adrenergic beta-1 Cardiology and Cardiovascular Medicine business |
| Zdroj: | Heart (British Cardiac Society). 91(12) |
| ISSN: | 1468-201X |
| Popis: | The β-1 adrenoceptor (AR), and to a lesser extent the β-2 AR, mediate the effect of circulating catecholamines on the pumping efficiency of the heart through positive inotropic, chronotropic, and lusitropic effects. These responses are required to meet the demands for increased tissue blood flow, not only during exercise, but also in pathophysiological states such as heart failure. Yet, cardiac responsiveness to β-1 AR activation or blockade, especially in heart failure, displays significant variation between individuals.1 The discovery of two common polymorphisms within the β-1 AR gene supports the notion that part of this may be genetic in origin. These variants, 389R>G and 49S>G, affect the encoded amino acid sequence (switching arginine to glycine and serine to glycine, respectively) and have notable effects on β-1 AR signalling both in cell lines and in intact human myocardial tissue.2,3 In vivo, the failing myocardium with its down regulated β-1 AR function may be particularly affected by these polymorphisms. Here we confirm a previous report that heart failure patients awaiting transplant do have significantly different exercise capacities depending on their genotype status for the 389R>G β-1 AR polymorphism. To identify sufficient numbers of patients with severe left ventricular (LV) dysfunction, we retrospectively approached 167 living patients entered into the cardiac transplant programme … |
| Databáze: | OpenAIRE |
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