RT Journal Article
SR Electronic
T1 Genetic Variation in β-Adrenergic Receptors and Their Relationship to Susceptibility for Asthma and Therapeutic Response
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 557
OP 561
VO 29
IS 4
A1 Robert P. Erickson
A1 Penelope E. Graves
YR 2001
UL http://dmd.aspetjournals.org/content/29/4/557.abstract
AB Our early work focused on quantitative variation in traits related to β-adrenergic signaling: lymphocyte levels of cAMP and the binding properties of the β-adrenergic receptor. We confirmed the work of others that the major histocompatibility locus had an effect on cAMP levels in mice and in man. The latter result was presumably due to the influence of β-adrenergic receptors, since it was the isoproterenol-stimulated lymphocyte cAMP level that was studied. We went on to directly study β-adrenergic receptor levels in mouse hepatic plasma membranes using dihydroalprenolol binding. We discovered a strain variation, apparently controlled by a single locus, which determined a magnesium influence on measurable levels of dihydroalprenolol binding. More recently, our group's work has focused on the human single nucleotide polymorphisms (SNPs) in the human β2-adrenergic receptor. We found that variation at amino acid position 16 had a very marked effect on the response of subjects to albuterol. Similar trends were observed for asthmatic and nonasthmatic children, and the results were independent of baseline lung function. Our results, and those of other groups relating SNPs in the β-adrenergic receptor to a number of responses, mostly related to asthma, are reviewed in this article. The American Society for Pharmacology and Experimental Therapeutics