Beta-adrenoceptor polymorphisms do not appear to be disease-causing genes for cardiovascular diseases, but they may act as risk factors, modify disease progression, and influence drug responses.
At present, nine adrenoceptor (AR) subtypes have been identified: alpha(1A)-, alpha(1B)-, alpha(1D)-, alpha(2A)-, alpha(2B)-, alpha(2C)-, beta(1)-, beta(2)-, and beta(3)AR. In the human heart, beta(1)- and beta(2)AR are the most powerful physiologic mechanism to acutely increase cardiac performance. Changes in betaAR play an important role in chronic heart failure (CHF). Thus, due to increased sympathetic activity in CHF, betaAR are chronically (over)stimulated, and that results in beta(1)AR desensitization and alterations of down-stream mechanisms. However, several questions remain open: What is the role of beta(2)AR in CHF? What is the role of increases in cardiac G(i)-protein in CHF? Do increases in G-protein-coupled receptor kinase (GRK)s play a role in CHF? Does betaAR-blocker treatment cause its beneficial effects in CHF, at least partly, by reducing GRK-activity? In this review these aspects of cardiac AR pharmacology in CHF are discussed. In addition, new insights into the functional importance of beta(1)- and beta(2)AR gene polymorphisms are discussed. At present it seems that for cardiovascular diseases, betaAR polymorphisms do not play a role as disease-causing genes; however, they might be risk factors, might modify disease, and/or might influence progression of disease. Furthermore, betaAR polymorphisms might influence drug responses. Thus, evidence has accumulated that a beta(1)AR polymorphism (the Arg389Gly beta(1)AR) may affect the response to betaAR-blocker treatment.
Brodde et al. (Sun,) conducted a review in Chronic heart failure. Beta-adrenoceptor polymorphisms was evaluated. Beta-adrenoceptor polymorphisms do not appear to be disease-causing genes for cardiovascular diseases, but they may act as risk factors, modify disease progression, and influence drug responses.