Beta-adrenergic receptor polymorphism in human cardiovascular disease.

Beta-adrenoceptors are polymorphic. Two common polymorphisms in the beta1-adrenoceptor (Ser49Gly and Arg389Gly) and three in the beta2-adrenoceptor (Arg16Gly, Gln27Glu, and Thr164Ile) appear to influence receptor function. In vitro studies of agonist-stimulation have shown that the Gly49 beta1-adrenoceptor and the Gly16 beta2-adrenoceptors are more susceptible to down-regulation, while the Glu27 beta2-adrenoceptor variant seems to be resistant. Whereas the Arg389 beta1-adrenoceptor demonstrates increased responsiveness to agonist stimulation in vitro, the Ile164 beta2-adrenoceptor variant, on the other hand, exhibits a decreased responsiveness. Although several studies in humans (ex vivo and in vivo) do support those functional effects, the literature on the phenotypic consequences of these beta-adrenoceptor polymorphisms in vivo is still far from being conclusive. At present, it appears that these beta-adrenoceptor polymorphisms are very likely not disease-causing genes, but might be risk factors, might modify disease and/or might influence progression of disease.