beta-Adrenergic receptor polymorphisms: relationship to the beta-agonist controversy and clinical implications

Aspects of the 'beta-agonist controversy' have recently re-emerged with the publication of data implicating the long-acting beta-agonist salmeterol in increased mortality from asthma. The reasons underlying the adverse effects of beta2-agonists as a class are unclear. Polymorphisms of the beta2 adrenoceptor (ADRB2), notably the variant associated with an arginine moiety at position 16 of the ADRB2 protein result in changes in in vitro receptor function. There is now consistent clinical evidence showing that, in vivo, patients with asthma harbouring the Arg-16 genotype may experience reduced lung function and an increased frequency of exacerbations when treated with regular short-acting beta-agonists. This may, in part, explain why beta-agonists have been associated with adverse outcomes in the past. ADRB2 genotyping of patients with severe or difficult-to-control asthma may shed light on a possible contributor to their clinical instability.