β 2 -Adrenergic Receptor Gene Affects the Heart Rate Response of β-Blockers: Evidence From 3 Clinical Studies.

Autor: Shahin MH; Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, FL, USA., Rouby NE; Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, FL, USA., Conrado DJ; Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, USA., Gonzalez D; Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA., Gong Y; Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, FL, USA., Lobmeyer MT; Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, FL, USA., Beitelshees AL; Department of Medicine, University of Maryland, Baltimore, MD, USA., Boerwinkle E; Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX, USA., Gums JG; Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, FL, USA., Chapman A; Department of Medicine, The University of Chicago, Chicago, IL, USA., Turner ST; Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA., Pepine CJ; Division of Cardiovascular Medicine, Department of Medicine, University of Florida, College of Medicine, Gainesville, FL, USA., Cooper-DeHoff RM; Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, FL, USA.; Division of Cardiovascular Medicine, Department of Medicine, University of Florida, College of Medicine, Gainesville, FL, USA., Johnson JA; Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, FL, USA.; Division of Cardiovascular Medicine, Department of Medicine, University of Florida, College of Medicine, Gainesville, FL, USA.
Jazyk: angličtina
Zdroj: Journal of clinical pharmacology [J Clin Pharmacol] 2019 Nov; Vol. 59 (11), pp. 1462-1470. Date of Electronic Publication: 2019 May 14.
DOI: 10.1002/jcph.1443
Abstrakt: β-Blockers' heart rate (HR)-lowering effect is an important determinant of the effectiveness for this class of drugs, yet it is variable among β-blocker-treated patients. To date, genetic studies have revealed several genetic signals associated with HR response to β-blockers. However, these genetic signals have not been consistently replicated across multiple independent cohorts. Here we sought to use data from 3 hypertension clinical trials to validate single-nucleotide polymorphisms (SNPs) previously associated with the HR response to β-blockers. Using linear regression analysis, we investigated the effects of 6 SNPs in 3 genes, including ADRB1, ADRB2, and GNB3, relative to the HR response following β-blocker used in the PEAR (n = 757), PEAR-2 (n = 368), and INVEST (n = 1401) trials, adjusting for baseline HR, age, sex, and ancestry. Atenolol was used in PEAR and INVEST, and metoprolol was used in PEAR-2. We found that rs1042714 and rs1042713 in ADRB2 were significantly associated with HR response to both β-blockers in whites (rs1042714 C-allele carriers, meta-analysis β = -0.95 beats per minute [bpm], meta-analysis P = 3×10 -4 ; rs1042713 A-allele carriers, meta-analysis β = -1.15 bpm, meta-analysis P = 2×10 -3 ). In conclusion, the results of our analyses provide strong evidence to support the hypothesis that rs1042714 and rs1042713 in the ADRB2 gene are important predictors of HR response to cardioselective β-blockade in hypertensive patient cohorts.
(© 2019, The American College of Clinical Pharmacology.)
Databáze: MEDLINE
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