Pharmacogenetics of the β2-Adrenergic Receptor Gene

Abstract

Asthma is a complex genetic disease with multiple genetic and environmental determinants contributing to the observed variability in response to common anti-asthma therapies. Asthma pharmacogenetic research has focused on multiple candidate genes including the β2-adrenergic receptor gene (ADRβ2) and its effect on individual responses to beta agonist therapy. At present, knowledge about the effects of ADRβ2 variation on therapeutic responses is evolving and should not alter current Asthma Guideline approaches consisting of the use of short acting beta agonists for as-needed symptom based therapy and the use of a regular long-acting beta agonist in combination with inhaled corticosteroid therapy for optimal control of asthma symptoms in those asthmatics who are not controlled on inhaled corticosteroid alone. This approach is based upon studies showing a consistent pharmacogenetic response to regular use of short acting beta agonists (SABA) and less consistent findings in studies evaluating long acting beta agonist (LABA). While emerging pharmacogenetic studies are provocative and should lead to functional approaches, conflicting data with responses to LABA therapy may be caused by factors that include small sample sizes of study populations and differences in experimental design that may limit the conclusions that may be drawn from these clinical trials at the present time.

Pharmacogenetics: Implications of race and ethnicity on defining genetic profiles for personalized medicine

“…59,60 Additional ADRB2 polymorphisms have been identified in most ethnic groups include additional coding variants (Cys 19(BUP) Arg, Gln 27 Glu, Thr 164 Ile) with varying allele frequencies resulting in complex haplotypes, some of which are specific to certain ethnic groups. 57,58,61 …”

Pharmacogenomics of long-acting β2-agonists

“…Data taken from [89]. Reproduced with permission from [11] copyright Ó John Wiley and Sons and from [147] with permission of Elsevier. homozygous for Arg-19 are most often homozygous for Gly16-Glu27 [90].…”

Pharmacogenetics of beta2 adrenergic receptor agonists in asthma management

“…Over 49 polymorphisms or variants have been identified in asthmatics from different ethnic groups and include SNPs, polynucleotide insertion–deletions, and polynucleotide repeats . ADRB2 pharmacogenetics has been reviewed elsewhere .…”

“…The most studied ADRB2 polymorphism is a common coding variant, Gly 16 Arg . In vitro , receptors with the Gly 16 variant have enhanced beta agonist‐induced receptor downregulation compared to receptors with Arg 16 .…”