Beta‐adrenergic receptor polymorphism in human cardiovascular disease

Abstract

Beta‐adrenoceptors are polymorphic. Two common polymorphisms in the β ₁ ‐adrenoceptor (Ser49Gly and Arg389Gly) and three in the β ₂ ‐adrenoceptor (Arg16Gly, Gln27Glu, and Thr164Ile) appear to influence receptor function. In vitro studies of agonist‐stimulation have shown that the Gly49 β ₁ ‐adrenoceptor and the Gly16 β ₂ ‐adrenoceptors are more susceptible to down‐regulation, while the Glu27 β ₂ ‐adrenoceptor variant seems to be resistant. Whereas the Arg389 β ₁ ‐adrenoceptor demonstrates increased responsiveness to agonist stimulation in vitro, the Ile164 β ₂ ‐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 β‐adrenoceptor polymorphisms in vivo is still far from being conclusive. At present, it appears that these β‐adrenoceptor polymorphisms are very likely not disease‐causing genes, but might be risk factors, might modify disease and/or might influence progression of disease.

• β‐adrenoceptors
• genotype
• haplotype
• linkage disequilibrium
• phenotype
• single nucleotide polymorphism