Very important pharmacogene summary ADRB2

Abstract

The beta2-adrenergic receptor (beta2-AR) is a member of the G-protein-coupled adrenergic receptor family with seven transmembrane segments. Similar to other members of this receptor family, beta2-AR specifically binds and is activated by the endogenous class of ligands known as catecholamines, and epinephrine in particular. The gene encoding this receptor, ADRB2, was cloned by Kobilka et al. in 1987 and is localized to chromosome 5q31–q32, a region that has been linked with asthma and asthma related phenotypes [1,2]. ADRB2 consists of a single exon of 2015 nucleotides, which encodes a 413 amino acid protein. This review highlights the genetic polymorphisms in ADRB2 and the pivotal role of beta2- AR in the regulation of the cardiac, pulmonary, vascular, endocrine, and central nervous systems. ADRB2 is abundantly expressed in bronchial smooth muscle cells and activation of the resulting receptor leads to bronchodilation. In addition, this gene is expressed in cardiac myocytes and vascular smooth muscle cells. Activation of beta2-AR in these cells causes an increase in the rate and force of heart contractions. Intracellular signaling upon beta2-AR activation is largely affected through a trimer of G proteins coupled to adenylate cyclase, to produce cyclic adenosine monophosphate. This, in turn, activates protein kinase A, leading to the phosphorylation and down-regulation of proteins including beta2-AR itself (please refer to PharmGKB β-agonist and β-blocker Pathway for further details: https://www.pharmgkb.org/do/serve?objId=PA2024&objCls=Pathway#). Beta2-AR is the target of clinically important drugs for asthma and cardiovascular conditions including hypertension and congestive heart failure (CHF). Beta-receptor agonists (e.g. albuterol, salmeterol) and antagonists (e.g. carvedilol and propranolol) are among the most commonly prescribed medications in the treatment of asthma and cardiovascular disease, respectively. Although some beta-blockers are ‘selective’ for the beta1-AR (e.g. metoprolol and atenolol), these also antagonize the beta2-AR at higher concentrations. A number of genetic polymorphisms in the ADRB2 gene have been described which affect gene expression, the function of the resulting receptor, and response to beta2-agonists.