Beschreibung:
<jats:title>Abstract</jats:title><jats:p>β<jats:sub>1</jats:sub>‐ and β<jats:sub>2</jats:sub>‐Adrenoceptors (AR) play a pivotal role in regulation of the cardiovascular system. Both β‐AR subtypes are polymorphic. There are two major single nucleotide polymorphisms (SNPs) in the β<jats:sub>1</jats:sub>‐AR gene: the Ser49Gly and Arg389Gly β<jats:sub>1</jats:sub>‐AR polymorphisms. In vitro, in recombinant cell systems Gly49 β<jats:sub>1</jats:sub>‐AR is much more susceptible to agonist‐promoted downregulation than Ser49 β<jats:sub>1</jats:sub>‐AR, while Arg389 β<jats:sub>1</jats:sub>‐AR is three to four times more responsive to agonist‐evoked stimulation than Gly389 β<jats:sub>1</jats:sub>‐AR. There are three major SNPs in the β<jats:sub>2</jats:sub>‐AR gene: the Arg16Gly, Gln27Glu and Thr164Ile β<jats:sub>2</jats:sub>‐AR polymorphisms (occur in humans only in the heterozygous form). In recombinant cell systems Gly16 β<jats:sub>2</jats:sub>‐AR is much more susceptible to agonist‐promoted downregulation while Glu27 β<jats:sub>2</jats:sub>‐AR is rather resistant to agonist‐induced downregulation but only in combination with Arg16, that occurs naturally extremely rare. Thr164 β<jats:sub>2</jats:sub>‐AR is three to four times more responsive to agonist‐evoked stimulation than Ile164 β<jats:sub>2</jats:sub>‐AR. This review summarizes results from various studies on the possible relationship of these polymorphisms to cardiovascular diseases. At present it appears to be clear that, for cardiovascular diseases such as hypertension, coronary artery disease and chronic heart failure, β<jats:sub>1</jats:sub>‐ and β<jats:sub>2</jats:sub>‐AR polymorphisms do not play a role as disease‐causing genes; however, they might affect drug responses. Thus, it might be possible, by assessing the β<jats:sub>1</jats:sub>‐AR genotype, to predict responsiveness to β<jats:sub>1</jats:sub>‐AR agonist and ‐blocker treatment: patients homozygous for the Arg389 β<jats:sub>1</jats:sub>‐AR polymorphism should be good responders while patients homozygous for the Gly389 β<jats:sub>1</jats:sub>‐AR polymorphism should be poor responders or non‐responders. Furthermore, subjects heterozygous for the Thr164Ile β<jats:sub>2</jats:sub>‐AR polymorphism exhibit blunted responses to β<jats:sub>2</jats:sub>‐AR stimulation. Finally, the Arg16Gln27 β<jats:sub>2</jats:sub>‐AR haplotype appears to be – at least in human vascular and bronchial smooth muscles – rather susceptible to agonist‐induced desensitization (in contrast to the recombinant cell system findings), and might have some predictive value for poor outcome of heart failure. However, future large prospective studies have to replicate these findings in order to substantiate their clinical relevance.</jats:p>