Biomaterial Database

Pharmacogenetic factors affecting β-blocker metabolism and response. 2020

Cameron D Thomas, and Julie A Johnson

Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida , Gainesville, FL, USA.

BACKGROUND β-blockers are among the most widely prescribed of all drugs, used for treatment of a large number of cardiovascular diseases. Herein we evaluate literature pertaining to pharmacogenetics of β-blocker therapy, provide insight into the robustness of the genetic associations, and determine the appropriateness for translating these genetic associations into clinical practice. METHODS A literature search was conducted using PubMed to collate evidence on associations between CYP2D6, ADRB1, ADRB2, and GRK5 genetic variation and drug-response outcomes in the presence of β-blocker exposure. Pharmacokinetic, pharmacodynamic, and clinical outcomes studies were included if genotype data and β-blocker exposure were documented. CONCLUSIONS Substantial data suggest that specific ADRB1 and GRK5 genotypes are associated with improved β-blocker efficacy and have potential for use to guide therapy decisions in the clinical setting. While the data do not justify ordering a CYP2D6 pharmacogenetic test, if CYP2D6 genotype is available in the electronic health record, there may be clinical utility for understanding dosing of β-blockers.

UI	MeSH Term	Description	Entries
D010597	Pharmacogenetics	A branch of genetics which deals with the genetic variability in individual responses to drugs and drug metabolism (BIOTRANSFORMATION).	Pharmacogenomics
D002318	Cardiovascular Diseases	Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.	Adverse Cardiac Event,Cardiac Events,Major Adverse Cardiac Events,Adverse Cardiac Events,Cardiac Event,Cardiac Event, Adverse,Cardiac Events, Adverse,Cardiovascular Disease,Disease, Cardiovascular,Event, Cardiac
D005838	Genotype	The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.	Genogroup,Genogroups,Genotypes
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000071185	Pharmacogenomic Testing	The detection of genetic variability (e.g., PHARMACOGENOMIC VARIANTS) relevant to PHARMACOGENETICS and PRECISION MEDICINE. The purpose of such genetic testing is to help determine the most effective treatment options and their optimum dosages with least potential risks for DRUG-RELATED SIDE EFFECTS AND ADVERSE REACTIONS.	Pharmacogenetic Analysis,Pharmacogenetic Screening,Pharmacogenetic Study,Pharmacogenetic Testing,Pharmacogenomic Analysis,Pharmacogenomic Screening,Pharmacogenomic Study,Pharmacogenetic Analyses,Pharmacogenetic Screenings,Pharmacogenetic Studies,Pharmacogenetic Testings,Pharmacogenomic Analyses,Pharmacogenomic Screenings,Pharmacogenomic Studies,Pharmacogenomic Testings,Studies, Pharmacogenetic
D000319	Adrenergic beta-Antagonists	Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety.	Adrenergic beta-Antagonist,Adrenergic beta-Receptor Blockader,Adrenergic beta-Receptor Blockaders,beta-Adrenergic Antagonist,beta-Adrenergic Blocker,beta-Adrenergic Blocking Agent,beta-Adrenergic Blocking Agents,beta-Adrenergic Receptor Blockader,beta-Adrenergic Receptor Blockaders,beta-Adrenoceptor Antagonist,beta-Blockers, Adrenergic,beta-Adrenergic Antagonists,beta-Adrenergic Blockers,beta-Adrenoceptor Antagonists,Adrenergic beta Antagonist,Adrenergic beta Antagonists,Adrenergic beta Receptor Blockader,Adrenergic beta Receptor Blockaders,Adrenergic beta-Blockers,Agent, beta-Adrenergic Blocking,Agents, beta-Adrenergic Blocking,Antagonist, beta-Adrenergic,Antagonist, beta-Adrenoceptor,Antagonists, beta-Adrenergic,Antagonists, beta-Adrenoceptor,Blockader, Adrenergic beta-Receptor,Blockader, beta-Adrenergic Receptor,Blockaders, Adrenergic beta-Receptor,Blockaders, beta-Adrenergic Receptor,Blocker, beta-Adrenergic,Blockers, beta-Adrenergic,Blocking Agent, beta-Adrenergic,Blocking Agents, beta-Adrenergic,Receptor Blockader, beta-Adrenergic,Receptor Blockaders, beta-Adrenergic,beta Adrenergic Antagonist,beta Adrenergic Antagonists,beta Adrenergic Blocker,beta Adrenergic Blockers,beta Adrenergic Blocking Agent,beta Adrenergic Blocking Agents,beta Adrenergic Receptor Blockader,beta Adrenergic Receptor Blockaders,beta Adrenoceptor Antagonist,beta Adrenoceptor Antagonists,beta Blockers, Adrenergic,beta-Antagonist, Adrenergic,beta-Antagonists, Adrenergic,beta-Receptor Blockader, Adrenergic,beta-Receptor Blockaders, Adrenergic
D054774	G-Protein-Coupled Receptor Kinase 5	A G-protein-coupled receptor kinase subtype that is primarily expressed in the MYOCARDIUM and may play a role in the regulation of cardiac functions.	GRK5 Kinase,G Protein Coupled Receptor Kinase 5
D018342	Receptors, Adrenergic, beta-1	A subclass of beta-adrenergic receptors (RECEPTORS, ADRENERGIC, BETA). The adrenergic beta-1 receptors are equally sensitive to EPINEPHRINE and NOREPINEPHRINE and bind the agonist DOBUTAMINE and the antagonist METOPROLOL with high affinity. They are found in the HEART, juxtaglomerular cells, and in the central and peripheral nervous systems.	Adrenergic beta-1 Receptor,Adrenergic beta-1 Receptors,Receptors, beta-1 Adrenergic,beta-1 Adrenergic Receptors,Adrenergic Receptor, beta-1,Receptor, Adrenergic, beta-1,beta 1 Adrenergic Receptor,Adrenergic Receptor, beta 1,Adrenergic Receptors, beta-1,Adrenergic beta 1 Receptor,Adrenergic beta 1 Receptors,Receptor, Adrenergic beta-1,Receptor, beta-1 Adrenergic,Receptors, Adrenergic beta-1,Receptors, beta 1 Adrenergic,beta 1 Adrenergic Receptors,beta-1 Adrenergic Receptor,beta-1 Receptor, Adrenergic,beta-1 Receptors, Adrenergic