Synergistic Polymorphisms of β1- and α2C-Adrenergic Receptors and the Risk of Congestive Heart Failure
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Open Access
- 10 October 2002
- journal article
- research article
- Published by Massachusetts Medical Society in New England Journal of Medicine
- Vol. 347 (15) , 1135-1142
- https://doi.org/10.1056/nejmoa020803
Abstract
Sustained cardiac adrenergic stimulation has been implicated in the development and progression of heart failure. Release of norepinephrine is controlled by negative feedback from presynaptic α2-adrenergic receptors, and the targets of the released norepinephrine on myocytes are β1-adrenergic receptors. In transfected cells, a polymorphic α2C-adrenergic receptor (α2CDel322–325) has decreased function, and a variant of the β1-adrenergic receptor (β1Arg389) has increased function. We hypothesized that this combination of receptor variants, which results in increased synaptic norepinephrine release and enhanced receptor function at the myocyte, would predispose persons to heart failure.Keywords
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