This rare variant in β2-Adrenoceptor has only reported heterozygously (in 2-4% of the population) and strongly decreases the protein’s responsiveness to inducing compounds (agonists). Carriers of this variant are less sensitive to induction of increased heart rate, heart contraction, and vasodilation by β-AR agonists. Mixed data suggests that this variant does not have a significant impact on hypertension or heart disease. It may affect responsiveness to beta blocker drugs.
Polyphen 2 predicts benign effect.
Reduced agonist binding, reduced G-protein coupling and sequestration responses. In vivo human data shows reduced response to agonist effect on heart rate and contraction.
See Green SA et al. 1993 (7901205), Brodde OE 2008 (18353108).
Mixed data means the effect of this variant on disease is unclear.
See Brodde OE 2008 (18353108).
Unknown what effect, if any, this variant has on disease or drug effect.
No recommended treatment for this variant.
Low clinical importance, Uncertain pharmacogenetic
(The "low clinical importance, uncertain" qualifier is assigned automatically based on the above evidence and importance scores.)
Summary of published research, and additional commentary
Green SA, Cole G, Jacinto M, Innis M, Liggett SB. A polymorphism of the human
beta 2-adrenergic receptor within the fourth transmembrane domain alters ligand
binding and functional properties of the receptor. J Biol Chem. 1993 Nov
5;268(31):23116-21. PubMed PMID: 7901205.
This variant is reported to have much lower binding affinities to agonists epinephrine, isoproterenol and norepinephrine. In addition, antagonists without aromatic ring polar substituents displayed a decreased affinity. Functional coupling to G-protein and sequestration in response to agonists were also reduced.
Brodde OE. Beta1- and beta2-adrenoceptor polymorphisms and cardiovascular
diseases. Fundam Clin Pharmacol. 2008 Apr;22(2):107-25. Review. PubMed PMID:
Review article of studies on the effect of this and other variants in the gene. Conflicting results for an effect on hypertension and coronary heart disease leads the author to conclude: “similar to β1-AR, β2-AR polymorphisms do not seem to be disease-causing genes in hypertension or in CHF but they might affect drug responses.” The variant is described as having a significant effect in vitro, and other variants in the gene have been reported to affect responsiveness to beta blockers.
hu9385BA - CGI sample GS00253-DNA_E01_200_37
het T @ chr5:148206885
huA90CE6 - PGP16 (huA90CE6) build 37, from CGI var (software ver 22.214.171.124), CGI sample GS000006909
het T @ chr5:148206885