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β2 -Adrenergic Receptor Gene Affects the Heart Rate Response of β-Blockers: Evidence From 3 Clinical Studies.

Publication ,  Journal Article
Shahin, MH; Rouby, NE; Conrado, DJ; Gonzalez, D; Gong, Y; Lobmeyer, MT; Beitelshees, AL; Boerwinkle, E; Gums, JG; Chapman, A; Turner, ST ...
Published in: J Clin Pharmacol
November 2019

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.

Duke Scholars

Published In

J Clin Pharmacol

DOI

EISSN

1552-4604

Publication Date

November 2019

Volume

59

Issue

11

Start / End Page

1462 / 1470

Location

England

Related Subject Headings

  • White People
  • Receptors, Adrenergic, beta-2
  • Receptors, Adrenergic, beta-1
  • Polymorphism, Single Nucleotide
  • Pharmacology & Pharmacy
  • Middle Aged
  • Metoprolol
  • Male
  • Hypertension
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
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Shahin, M. H., Rouby, N. E., Conrado, D. J., Gonzalez, D., Gong, Y., Lobmeyer, M. T., … Johnson, J. A. (2019). β2 -Adrenergic Receptor Gene Affects the Heart Rate Response of β-Blockers: Evidence From 3 Clinical Studies. J Clin Pharmacol, 59(11), 1462–1470. https://doi.org/10.1002/jcph.1443
Shahin, Mohamed H., Nihal El Rouby, Daniela J. Conrado, Daniel Gonzalez, Yan Gong, Maximilian T. Lobmeyer, Amber L. Beitelshees, et al. “β2 -Adrenergic Receptor Gene Affects the Heart Rate Response of β-Blockers: Evidence From 3 Clinical Studies.J Clin Pharmacol 59, no. 11 (November 2019): 1462–70. https://doi.org/10.1002/jcph.1443.
Shahin MH, Rouby NE, Conrado DJ, Gonzalez D, Gong Y, Lobmeyer MT, et al. β2 -Adrenergic Receptor Gene Affects the Heart Rate Response of β-Blockers: Evidence From 3 Clinical Studies. J Clin Pharmacol. 2019 Nov;59(11):1462–70.
Shahin, Mohamed H., et al. “β2 -Adrenergic Receptor Gene Affects the Heart Rate Response of β-Blockers: Evidence From 3 Clinical Studies.J Clin Pharmacol, vol. 59, no. 11, Nov. 2019, pp. 1462–70. Pubmed, doi:10.1002/jcph.1443.
Shahin MH, Rouby NE, Conrado DJ, Gonzalez D, Gong Y, Lobmeyer MT, Beitelshees AL, Boerwinkle E, Gums JG, Chapman A, Turner ST, Pepine CJ, Cooper-DeHoff RM, Johnson JA. β2 -Adrenergic Receptor Gene Affects the Heart Rate Response of β-Blockers: Evidence From 3 Clinical Studies. J Clin Pharmacol. 2019 Nov;59(11):1462–1470.

Published In

J Clin Pharmacol

DOI

EISSN

1552-4604

Publication Date

November 2019

Volume

59

Issue

11

Start / End Page

1462 / 1470

Location

England

Related Subject Headings

  • White People
  • Receptors, Adrenergic, beta-2
  • Receptors, Adrenergic, beta-1
  • Polymorphism, Single Nucleotide
  • Pharmacology & Pharmacy
  • Middle Aged
  • Metoprolol
  • Male
  • Hypertension
  • Humans