Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC) for CYP2D6, ADRB1, ADRB2, ADRA2C, GRK4, and GRK5 Genotypes and Beta-Blocker Therapy

Document Type

Article

Publication Date

10-1-2024

Publication Title

Clinical pharmacology and therapeutics

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).

Medical Subject Headings

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

PubMed ID

38951961

ePublication

ePub ahead of print

Volume

116

Issue

4

First Page

939

Last Page

947

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