Polymorphisms determine β-adrenoceptor conformation: implications for cardiovascular disease and therapy

β₁- and β₂-adrenoceptors are crucial regulators of cardiovascular function. Agonists and antagonists at these receptor subtypes are cornerstones in the treatment of cardiovascular disease. In humans, both of the genes encoding the β₁- and β₂-adrenoceptors carry frequent polymorphisms resulting in different variants of the receptor proteins. Whether the polymorphic nature of the receptors causes the clinically observed differences with respect to the response of the patients to therapeutic drugs is currently a matter of intense discussion. Here, we discuss recent progress regarding the determination of β-adrenoceptor conformational changes and how these can help to clarify this issue. Specifically, novel optical methods enable us to directly assess the functional importance of β-adrenoceptor polymorphisms on ligand-induced changes of receptor conformation. The ability to determine polymorphism-dependent differences in drug efficacy directly on the receptor level might develop into an important approach to establish individualized drug therapies based on the genetic determinants of the patients.