{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:05:09Z","timestamp":1792800309017,"version":"4.5.0"},"reference-count":56,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:p>Beta\u2010blockers are widely used medications for a variety of indications, including heart failure, myocardial infarction, cardiac arrhythmias, and hypertension. Genetic variability in pharmacokinetic (e.g., <jats:italic>CYP2D6<\/jats:italic>) and pharmacodynamic (e.g., <jats:italic>ADRB1<\/jats:italic>, <jats:italic>ADRB2<\/jats:italic>, <jats:italic>ADRA2C<\/jats:italic>, <jats:italic>GRK4<\/jats:italic>, <jats:italic>GRK5<\/jats:italic>) genes have been studied in relation to beta\u2010blocker exposure and response. We searched and summarized the strength of the evidence linking beta\u2010blocker exposure and response with the six genes listed above. The level of evidence was high for associations between <jats:italic>CYP2D6<\/jats:italic> 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. 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Michael","family":"Stein","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine Vanderbilt University Medical Center  Nashville Tennessee USA"},{"name":"Department of Pharmacology Vanderbilt University School of Medicine  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8928-7049","authenticated-orcid":false,"given":"Chakradhara Rao S.","family":"Uppugunduri","sequence":"additional","affiliation":[{"name":"Division of Pediatric Oncology and Hematology, Department of Women, Child and Adolescent University Geneva Hospitals  Geneva Switzerland"},{"name":"Department of Pediatrics, Gynecology and Obstetrics, Cansearch Research Platform for Pediatric Oncology and Hematology, Faculty of Medicine University of Geneva  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1864-2151","authenticated-orcid":false,"given":"Ron H. N.","family":"van Schaik","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry Erasmus MC University Medical Center  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7550-042X","authenticated-orcid":false,"given":"Roseann S.","family":"Donnelly","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice Massachusetts College of Pharmacy and Health Sciences  Boston Massachusetts USA"},{"name":"Department of Pharmacy and Pharmaceutical Sciences St. Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5663-3793","authenticated-orcid":false,"given":"Kelly E.","family":"Caudle","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Sciences St. Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3639-717X","authenticated-orcid":false,"given":"Jasmine A.","family":"Luzum","sequence":"additional","affiliation":[{"name":"Center for Individualized and Genomic Medicine Research (CIGMA), Henry Ford Hospital  Detroit Michigan USA"},{"name":"Department of Clinical Pharmacy University of Michigan College of Pharmacy  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7]]},"reference":[{"key":"e_1_2_11_1_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1643"},{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2321"},{"key":"e_1_2_11_3_1","unstructured":"CPIC.CPIC\u00ae guideline for beta\u2010blockers and CYP2D6 ADRB1 ADRB2 GRK4 and GRK5. <https:\/\/cpicpgx.org\/guidelines\/cpic\u2010guideline\u2010for\u2010beta\u2010blockers\/> Accessed July 20 2022."},{"key":"e_1_2_11_4_1","unstructured":"PharmGKB.Gene\u2010specific information tables for CYP2D6. <https:\/\/www.pharmgkb.org\/page\/cyp2d6RefMaterials> Accessed July 20 2022."},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.3044"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.24.16701"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2009.00185.x"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1159\/000395473"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)37910-4"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ph.43.030181.003205"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2005.02438.x"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198207223070401"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa010819"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.13.1.7598936"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00198a006"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/46040"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M000796200"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/01213011-200503000-00002"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.63.1.9"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.062694599"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)37451-3"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1750"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12692"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.00520"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.119.007012"},{"key":"e_1_2_11_26_1","article-title":"Validation of a polygenic score for Beta\u2010blocker survival benefit in patients with heart failure using the United Kingdom biobank","volume":"003835","author":"Lanfear D.E.","year":"2023","journal-title":"Circ. 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