ADRB1

ADRB1 is the gene that encodes the beta-1 adrenergic receptor (β1-AR), a member of the adrenergic receptor family of G protein–coupled receptors. The receptor binds the catecholamines epinephrine and norepinephrine with high affinity and is predominantly expressed in cardiac tissue, with lower levels reported in adipose tissue and certain brain regions.

Beta-1 adrenergic receptors signal through the stimulatory G protein (Gs), activating adenylyl cyclase to raise intracellular cyclic AMP. This leads to activation of protein kinase A and downstream effects that increase heart rate (positive chronotropy), enhance myocardial contractility (positive inotropy), and influence conduction velocity. In the heart, β1-AR signaling modulates the sympathetic response and supports the fight-or-flight reaction, with effects that are integrated with other receptors and signaling pathways.

Genetic variation in ADRB1 has been studied for associations with cardiovascular traits and pharmacologic response. Common variants include Arg389Gly and Ser49Gly. The Arg389 variant is often reported to have higher basal and agonist-stimulated activity, which may influence resting heart rate and responsiveness to beta-blocker therapy in some individuals. The Ser49Gly variant can affect receptor desensitization and downregulation in certain contexts. Overall, these polymorphisms have been explored for potential to predict outcomes in heart failure, hypertension, and treatment response, though findings are heterogeneous across populations.

Clinically, the β1-adrenergic receptor is a target of cardioselective beta-blockers such as metoprolol, bisoprolol, and atenolol, which reduce heart rate and myocardial oxygen demand. ADRB1 genetic status may contribute to interindividual variability in drug efficacy and tolerability, contributing to interests in pharmacogenetics for cardiovascular therapy.