Pharmacogenetic factors affecting β-blocker metabolism and response
Cameron D. Thomas, Julie A. Johnson
Abstract
Introduction 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.Areas covered 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.Expert opinion 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.