Document Type
Article
Publication Date
10-2024
Identifier
DOI: 10.1002/cpt.3351
Abstract
Beta-blockers are widely used medications for a variety of indications, including heart failure, myocardial infarction, cardiac arrhythmias, and hypertension. Genetic variability in pharmacokinetic (e.g., CYP2D6) and pharmacodynamic (e.g., ADRB1, ADRB2, ADRA2C, GRK4, GRK5) genes have been studied in relation to beta-blocker exposure and response. We searched and summarized the strength of the evidence linking beta-blocker exposure and response with the six genes listed above. The level of evidence was high for associations between CYP2D6 genetic variation and both metoprolol exposure and heart rate response. Evidence indicates that CYP2D6 poor metabolizers experience clinically significant greater exposure and lower heart rate in response to metoprolol compared with those who are not poor metabolizers. Therefore, we provide therapeutic recommendations regarding genetically predicted CYP2D6 metabolizer status and metoprolol therapy. However, there was insufficient evidence to make therapeutic recommendations for CYP2D6 and other beta-blockers or for any beta-blocker and the other five genes evaluated (updates at www.cpicpgx.org).
Journal Title
Clinical pharmacology and therapeutics
Volume
116
Issue
4
First Page
939
Last Page
947
MeSH Keywords
Humans; Cytochrome P-450 CYP2D6; Adrenergic beta-Antagonists; Receptors, Adrenergic, beta-2; G-Protein-Coupled Receptor Kinase 5; Receptors, Adrenergic, beta-1; Genotype; Pharmacogenetics; Receptors, Adrenergic, alpha-2; Metoprolol; Pharmacogenomic Variants
Keywords
Cytochrome P-450 CYP2D6; Adrenergic beta-Antagonists; Adrenergic Receptors, beta-2; G-Protein-Coupled Receptor Kinase 5; Adrenergic Receptors, beta-1; Genotype; Pharmacogenetics; Adrenergic Receptors, alpha-2; Metoprolol; Pharmacogenomic Variants
Recommended Citation
Duarte JD, Thomas CD, Lee CR, et al. Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC) for CYP2D6, ADRB1, ADRB2, ADRA2C, GRK4, and GRK5 Genotypes and Beta-Blocker Therapy. Clin Pharmacol Ther. 2024;116(4):939-947. doi:10.1002/cpt.3351
Comments
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Publisher's Link: https://ascpt.onlinelibrary.wiley.com/doi/10.1002/cpt.3351