Clinical consequences of ADRβ2 polymorphisms

The most prescribed medication for controlling bronchoconstriction associated with asthma and chronic obstructive pulmonary disease are β-agonists. The gene ADRβ2 encodes the β-2-adrenergic receptor and contains several common genetic variations that affect gene expression and receptor function in vitro. The ADRβ2 variations Gly¹⁶Arg and Gln²⁷Glu and, more recently, haplotypic variations, have been the focus of numerous pharmacogenetic studies looking at responses to short-acting (SABA) and long-acting β-agonists (LABA) in subjects with asthma. Thus far, a consensus on the effects of ADRβ2 genetic variations has not been reached, although there does appear to be a reproducible adverse effect in subjects homozygous for Arg¹⁶ that are regularly treated with SABAs. The complexity of the genotype by response effects observed makes clinical application of ADRβ2 genetic variations limited, and may require the use of detailed haplotypic variation to fully understand the role ADRβ2 plays in regulating β-agonist response.