Pharmacology and physiology of human adrenergic receptor polymorphisms

Adrenergic receptors are expressed on virtually every cell type in the body and are the receptors for epinephrine and norepinephrine within the sympathetic nervous system. They serve critical roles in maintaining homeostasis in normal physiologic settings as well as pathologic states. These receptors are also targets for therapeutically administered agonists and antagonists. Recent studies have shown that at least seven adrenergic receptor subtypes display variation in amino acid sequence in the human population due to common genetic polymorphisms. Variations in potential regulatory domains in noncoding sequence are also present. Here, we review the consequences of these polymorphisms in terms of signaling, human physiology and disease, and response to therapy.