Beta-adrenergic receptor polymorphisms and drug responses in asthma

Genetic variation in the beta 2-adrenoceptor and its associated proteins is common and therefore potentially relevant to the clinician. Several functional SNPs have been described but in vitro studies have yielded inconsistent results. Confounding due to the variable presence of other polymorphic alleles may be the explanation and the recent definition of ADRB2 haplotypes offers the opportunity for clarification. In vitro studies have concentrated on downregulation and desensitization as functional end points. However, the relevance of these phenomena is unclear and extrapolating in vitro data to the clinical setting may not be appropriate. To date, only the Arg(16) polymorphism appears to be important in determining beta 2-agonist drug responses but the data as well as their application are limited. The results of prospective studies based on selection by ADRB2 haplotype will be necessary before a more general application of this knowledge can be encouraged.