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

Julio D. Duarte; Cameron D. Thomas; Craig R. Lee; Rachel Huddart; Jose A. G. Agundez; Jordan F. Baye; Andrea Gaedigk; Teri E. Klein; David E. Lanfear; Andrew A. Monte; Mohamed Nagy; Matthias Schwab; C. Michael Stein; Chakradhara Rao S. Uppugunduri; Ron H. N. van Schaik; Roseann S. Donnelly; Kelly E. Caudle; Jasmine A. Luzum

doi:10.1002/cpt.3351

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

Julio D. Duarte^*, Cameron D. Thomas, Craig R. Lee, Rachel Huddart, Jose A. G. Agundez, Jordan F. Baye, Andrea Gaedigk, Teri E. Klein, David E. Lanfear, Andrew A. Monte, Mohamed Nagy, Matthias Schwab, C. Michael Stein, Chakradhara Rao S. Uppugunduri, Ron H. N. van Schaik, Roseann S. Donnelly, Kelly E. Caudle, Jasmine A. Luzum

^*Corresponding author for this work

Clinical Chemistry

Research output: Contribution to journal › Review article › Academic › peer-review

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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).

Original language	English
Number of pages	9
Journal	Clinical Pharmacology & Therapeutics
Early online date	1 Jul 2024
DOIs	https://doi.org/10.1002/cpt.3351
Publication status	E-pub ahead of print - 1 Jul 2024

Bibliographical note

Publisher Copyright:
© 2024 The Author(s). Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.

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Clin Pharma and Therapeutics - 2024 - Duarte - Clinical Pharmacogenetics Implementation Consortium Guideline CPIC forFinal published version, 278 KBLicence: CC BY-NC

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Duarte, J. D., Thomas, C. D., Lee, C. R., Huddart, R., Agundez, J. A. G., Baye, J. F., Gaedigk, A., Klein, T. E., Lanfear, D. E., Monte, A. A., Nagy, M., Schwab, M., Stein, C. M., Uppugunduri, C. R. S., van Schaik, R. H. N., Donnelly, R. S., Caudle, K. E., & Luzum, J. A. (2024). Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC) for CYP2D6, ADRB1, ADRB2, ADRA2C, GRK4, and GRK5 Genotypes and Beta-Blocker Therapy. Clinical Pharmacology & Therapeutics. Advance online publication. https://doi.org/10.1002/cpt.3351

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

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).",

author = "Duarte, {Julio D.} and Thomas, {Cameron D.} and Lee, {Craig R.} and Rachel Huddart and Agundez, {Jose A. G.} and Baye, {Jordan F.} and Andrea Gaedigk and Klein, {Teri E.} and Lanfear, {David E.} and Monte, {Andrew A.} and Mohamed Nagy and Matthias Schwab and Stein, {C. Michael} and Uppugunduri, {Chakradhara Rao S.} and {van Schaik}, {Ron H. N.} and Donnelly, {Roseann S.} and Caudle, {Kelly E.} and Luzum, {Jasmine A.}",

note = "Publisher Copyright: {\textcopyright} 2024 The Author(s). Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.",

year = "2024",

month = jul,

day = "1",

doi = "10.1002/cpt.3351",

language = "English",

journal = "Clinical Pharmacology & Therapeutics",

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Duarte, JD, Thomas, CD, Lee, CR, Huddart, R, Agundez, JAG, Baye, JF, Gaedigk, A, Klein, TE, Lanfear, DE, Monte, AA, Nagy, M, Schwab, M, Stein, CM, Uppugunduri, CRS, van Schaik, RHN, Donnelly, RS, Caudle, KE & Luzum, JA 2024, 'Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC) for CYP2D6, ADRB1, ADRB2, ADRA2C, GRK4, and GRK5 Genotypes and Beta-Blocker Therapy', Clinical Pharmacology & Therapeutics. https://doi.org/10.1002/cpt.3351

TY - JOUR

T1 - Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC) for CYP2D6, ADRB1, ADRB2, ADRA2C, GRK4, and GRK5 Genotypes and Beta-Blocker Therapy

AU - Duarte, Julio D.

AU - Thomas, Cameron D.

AU - Lee, Craig R.

AU - Huddart, Rachel

AU - Agundez, Jose A. G.

AU - Baye, Jordan F.

AU - Gaedigk, Andrea

AU - Klein, Teri E.

AU - Lanfear, David E.

AU - Monte, Andrew A.

AU - Nagy, Mohamed

AU - Schwab, Matthias

AU - Stein, C. Michael

AU - Uppugunduri, Chakradhara Rao S.

AU - van Schaik, Ron H. N.

AU - Donnelly, Roseann S.

AU - Caudle, Kelly E.

AU - Luzum, Jasmine A.

PY - 2024/7/1

Y1 - 2024/7/1

N2 - 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).

AB - 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).

UR - http://www.scopus.com/inward/record.url?scp=85197294153&partnerID=8YFLogxK

U2 - 10.1002/cpt.3351

DO - 10.1002/cpt.3351

M3 - Review article

C2 - 38951961

SN - 0009-9236

JO - Clinical Pharmacology & Therapeutics

JF - Clinical Pharmacology & Therapeutics

ER -

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

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