Clinical consequences of ADRbeta2 polymorphisms.
The most prescribed medication for controlling bronchoconstriction associated with asthma and chronic obstructive pulmonary disease are beta-agonists. The gene ADRbeta2 encodes the beta-2-adrenergic receptor and contains several common genetic variations that affect gene expression and receptor function in vitro. The ADRbeta2 variations Gly(16)Arg and Gln(27)Glu and, more recently, haplotypic variations, have been the focus of numerous pharmacogenetic studies looking at responses to short-acting (SABA) and long-acting beta-agonists (LABA) in subjects with asthma. Thus far, a consensus on the effects of ADRbeta2 genetic variations has not been reached, although there does appear to be a reproducible adverse effect in subjects homozygous for Arg(16) that are regularly treated with SABAs. The complexity of the genotype by response effects observed makes clinical application of ADRbeta2 genetic variations limited, and may require the use of detailed haplotypic variation to fully understand the role ADRbeta2 plays in regulating beta-agonist response.
Hawkins
Gregory A
GA
Center for Human Genomics, Section of Pulmonary, Critical Care, Allergy and Immunologic Diseases, Wake Forest University Health Sciences, Winston-Salem, NC 27157, USA. ghawkins@wfubmc.edu
Weiss
Scott T
ST
Bleecker
Eugene R
ER
D000318:Adrenergic beta-Agonists / Q000627:therapeutic use; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy / Q000235:genetics*; D001483:Base Sequence; D014644:Genetic Variation; D006801:Humans; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*
D000318:Adrenergic beta-Agonists; D018927:Anti-Asthmatic Agents; D018343:Receptors, Adrenergic, beta-2