• β1-Adrenoceptor;
  • β2-Adrenoceptor;
  • cardiovascular diseases;
  • genotype;
  • haplotype;
  • phenotype;
  • single nucleotide polymorphism

β1- and β2-Adrenoceptors (AR) play a pivotal role in the regulation of cardiovascular function. Both β-AR subtypes are polymorphic: two single nucleotide polymorphisms (SNPs) have been described for the β1- (Ser49Gly, Arg389Gly) and four for the β2-AR (Arg-19Cys, Arg16Gly, Gln27Glu, Thr164Ile), and they are possibly of functional relevance. In recombinant cell systems, Gly49-β1-AR are more susceptible to agonist-promoted down-regulation than Ser49-β1-AR, whereas Arg389-β1-AR are three to four times more responsive to agonist-evoked stimulation than Gly389-β1-AR. With respect to β2-AR, the Cys-19 variant is associated with greater β2-AR expression than the Arg-19 variant; Gly16-β2-AR are more susceptible, whereas Glu27-β2-AR are almost resistant to agonist-promoted down-regulation; Thr164-β2-AR are three to four times more responsive to agonist-evoked stimulation than Ile164-β2-AR. Several studies addressed potential phenotypic consequences of these SNPs in vivo by influencing and/or contributing to the pathophysiology of cardiovascular/pulmonary diseases such as hypertension, congestive heart failure, arrhythmias or asthma. At present, it appears that these β-AR SNPs are very likely not disease-causing genes but possibly predictive for the responsiveness to agonists and antagonists. Patients carrying one or two alleles of the Gly389-β1-AR are poor or non-responders to agonists and antagonists, whereas patients homozygous for the Arg389-β1-AR are good responders. Subjects carrying the Ile164-β2-AR exhibit blunted responses to β2-AR stimulation. Asthma patients carrying the Arg16-Gln27-Thr164-β2-AR haplotype who receive regularly short- or long-acting β2-AR agonists are rather susceptible to agonist-induced desensitization and in consequence exhibit reduced bronchodilating and -protective effects and/or increased asthma exacerbations. The clinical relevance of these findings is still under debate.