Β-AR polymorphisms and glycemic and lipid parameters in hypertensive individuals receiving carvedilol or metoprolol

Orly Vardeny, Gabriel Nicholas, Alina Andrei, Kevin A. Buhr, Matt P. Hermanson, John J. Moran, Michelle A. Detry, James H. Stein

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Background Β-Blocker therapy and Β-adrenergic receptor (Β-AR) polymorphisms are associated with increases in glucose and lipid levels. We investigated associations of common Β1 and Β2-AR single-nucleotide polymorphisms (SNPs) with metabolic and lipid variables, and examined interactions with Β-blocker treatment assignment to affect these parameters. Methods This was a post hoc analysis of a double-blinded clinical trial of nondiabetic, hypertensive individuals that were randomized to receive carvedilol or metoprolol succinate. Fasting glucose, insulin, and lipid levels were measured at baseline, 3 months, and after 6 months. Genotypes for Β1-AR SNPs Ser49Gly Gly389Arg and Β2-AR Arg16Gly Gln27Glu were determined. Multivariable mixed models were used to examine associations between Β-AR polymorphisms, metabolic parameters, and SNP interactions with Β-blocker therapy (p interaction). Results The 322 subjects were mean (s.d.) 51.5 (11.2) years old. After 6 months, insulin levels increased by 35.6% on metoprolol and 9.9% on carvedilol (P = 0.015). In univariate models, the Gln27Gln genotype had higher overall insulin levels with Β-blockade compared to the Glu27Glu genotype (P = 0.006). Both Arg16Gly (P = 0.012) and Gln27Glu (P = 0.037) SNPs were associated with higher triglycerides levels. An interaction between the Arg16Gly SNP and treatment was identified (p int = 0.048). Conclusions These data suggest that insulin and triglycerides may be influenced by Β2-AR polymorphisms in patients taking Β blockers.

Original languageEnglish (US)
Pages (from-to)920-926
Number of pages7
JournalAmerican journal of hypertension
Volume25
Issue number8
DOIs
StatePublished - Aug 2012
Externally publishedYes

Bibliographical note

Funding Information:
acknowledgment: this work was funded by glaxosmithKline and NIH 1uL1RR025011.

Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.

Keywords

  • blood pressure
  • hypertension
  • triglycerides
  • β-adrenergic receptor gene polymorphism
  • β-blocker

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