Genetic variation in the β2-adrenergic receptor

Impact on intermediate cardiovascular phenotypes

C. Hesse, John H. Eisenach

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Genetic variation in drug targets (e.g. receptors) can have pronounced effects on clinical responses to endogenous and exogenous agonists. Polymorphisms in the gene encoding the β2-adrenergic receptor (β2-AR) have been associated with altered expression, down-regulation, and altered cell signaling in vitro. Because β2-ARs play a crucial role in the regulation of the cardiovascular system, the functional importance of genetic variation in the β2-AR on cardiovascular responses to physiological or pharmacological stimuli has gained widespread attention. The objective of this review is to characterize these intermediate cardiovascular phenotypes and their influence on cardiovascular disease and adrenergic drug responses. Two common single nucleotide polymorphisms, encoded at codon 46 (Gly16Arg) and 79 (Gln27Glu) of the β2-AR gene, have been studied intensively. They have been shown to be associated with altered vasodilator responses to regional and systemic administration of β 2-agonists, altered cardiovascular responses to sympathoexcitatory maneuvers, and altered myocardial function. Importantly, these intermediate physiological patterns may influence the development of and the outcomes associated with hypertension and other cardiovascular diseases. As recently reported, β2-AR gene variation can risk-stratify patients receiving β-blocker therapy and may predict β-blocker efficacy in patients post acute coronary syndrome or in patients with heart failure. Further studies will advance our understanding of the link between β2-AR genotypes, intermediate cardiovascular phenotypes, and clinical phenotypes. In the long term, reassessment of the benefits of β-blocker-therapy within genotype groups should be carried out with the ultimate goal to design the optimal therapeutic regimen for the individual patient.

Original languageEnglish (US)
Pages (from-to)160-170
Number of pages11
JournalCurrent Pharmacogenomics and Personalized Medicine
Volume6
Issue number3
StatePublished - 2008

Fingerprint

Adrenergic Receptors
Phenotype
Cardiovascular Diseases
Genotype
Genes
Cardiovascular Agents
Acute Coronary Syndrome
Cardiovascular System
Vasodilator Agents
Codon
Adrenergic Agents
Single Nucleotide Polymorphism
Therapeutics
Down-Regulation
Heart Failure
Pharmacology
Hypertension
Pharmaceutical Preparations

Keywords

  • β-adrenergic receptor
  • Genotype
  • Haplotype
  • Phenotype
  • Polymorphism

ASJC Scopus subject areas

  • Genetics
  • Molecular Medicine
  • Pharmacology
  • Molecular Biology
  • Genetics(clinical)

Cite this

Genetic variation in the β2-adrenergic receptor : Impact on intermediate cardiovascular phenotypes. / Hesse, C.; Eisenach, John H.

In: Current Pharmacogenomics and Personalized Medicine, Vol. 6, No. 3, 2008, p. 160-170.

Research output: Contribution to journalArticle

@article{6f681feb936949c5b4b192bfc7264c20,
title = "Genetic variation in the β2-adrenergic receptor: Impact on intermediate cardiovascular phenotypes",
abstract = "Genetic variation in drug targets (e.g. receptors) can have pronounced effects on clinical responses to endogenous and exogenous agonists. Polymorphisms in the gene encoding the β2-adrenergic receptor (β2-AR) have been associated with altered expression, down-regulation, and altered cell signaling in vitro. Because β2-ARs play a crucial role in the regulation of the cardiovascular system, the functional importance of genetic variation in the β2-AR on cardiovascular responses to physiological or pharmacological stimuli has gained widespread attention. The objective of this review is to characterize these intermediate cardiovascular phenotypes and their influence on cardiovascular disease and adrenergic drug responses. Two common single nucleotide polymorphisms, encoded at codon 46 (Gly16Arg) and 79 (Gln27Glu) of the β2-AR gene, have been studied intensively. They have been shown to be associated with altered vasodilator responses to regional and systemic administration of β 2-agonists, altered cardiovascular responses to sympathoexcitatory maneuvers, and altered myocardial function. Importantly, these intermediate physiological patterns may influence the development of and the outcomes associated with hypertension and other cardiovascular diseases. As recently reported, β2-AR gene variation can risk-stratify patients receiving β-blocker therapy and may predict β-blocker efficacy in patients post acute coronary syndrome or in patients with heart failure. Further studies will advance our understanding of the link between β2-AR genotypes, intermediate cardiovascular phenotypes, and clinical phenotypes. In the long term, reassessment of the benefits of β-blocker-therapy within genotype groups should be carried out with the ultimate goal to design the optimal therapeutic regimen for the individual patient.",
keywords = "β-adrenergic receptor, Genotype, Haplotype, Phenotype, Polymorphism",
author = "C. Hesse and Eisenach, {John H.}",
year = "2008",
language = "English (US)",
volume = "6",
pages = "160--170",
journal = "Current Pharmacogenomics and Personalized Medicine",
issn = "1875-6921",
publisher = "Bentham Science Publishers B.V.",
number = "3",

}

TY - JOUR

T1 - Genetic variation in the β2-adrenergic receptor

T2 - Impact on intermediate cardiovascular phenotypes

AU - Hesse, C.

AU - Eisenach, John H.

PY - 2008

Y1 - 2008

N2 - Genetic variation in drug targets (e.g. receptors) can have pronounced effects on clinical responses to endogenous and exogenous agonists. Polymorphisms in the gene encoding the β2-adrenergic receptor (β2-AR) have been associated with altered expression, down-regulation, and altered cell signaling in vitro. Because β2-ARs play a crucial role in the regulation of the cardiovascular system, the functional importance of genetic variation in the β2-AR on cardiovascular responses to physiological or pharmacological stimuli has gained widespread attention. The objective of this review is to characterize these intermediate cardiovascular phenotypes and their influence on cardiovascular disease and adrenergic drug responses. Two common single nucleotide polymorphisms, encoded at codon 46 (Gly16Arg) and 79 (Gln27Glu) of the β2-AR gene, have been studied intensively. They have been shown to be associated with altered vasodilator responses to regional and systemic administration of β 2-agonists, altered cardiovascular responses to sympathoexcitatory maneuvers, and altered myocardial function. Importantly, these intermediate physiological patterns may influence the development of and the outcomes associated with hypertension and other cardiovascular diseases. As recently reported, β2-AR gene variation can risk-stratify patients receiving β-blocker therapy and may predict β-blocker efficacy in patients post acute coronary syndrome or in patients with heart failure. Further studies will advance our understanding of the link between β2-AR genotypes, intermediate cardiovascular phenotypes, and clinical phenotypes. In the long term, reassessment of the benefits of β-blocker-therapy within genotype groups should be carried out with the ultimate goal to design the optimal therapeutic regimen for the individual patient.

AB - Genetic variation in drug targets (e.g. receptors) can have pronounced effects on clinical responses to endogenous and exogenous agonists. Polymorphisms in the gene encoding the β2-adrenergic receptor (β2-AR) have been associated with altered expression, down-regulation, and altered cell signaling in vitro. Because β2-ARs play a crucial role in the regulation of the cardiovascular system, the functional importance of genetic variation in the β2-AR on cardiovascular responses to physiological or pharmacological stimuli has gained widespread attention. The objective of this review is to characterize these intermediate cardiovascular phenotypes and their influence on cardiovascular disease and adrenergic drug responses. Two common single nucleotide polymorphisms, encoded at codon 46 (Gly16Arg) and 79 (Gln27Glu) of the β2-AR gene, have been studied intensively. They have been shown to be associated with altered vasodilator responses to regional and systemic administration of β 2-agonists, altered cardiovascular responses to sympathoexcitatory maneuvers, and altered myocardial function. Importantly, these intermediate physiological patterns may influence the development of and the outcomes associated with hypertension and other cardiovascular diseases. As recently reported, β2-AR gene variation can risk-stratify patients receiving β-blocker therapy and may predict β-blocker efficacy in patients post acute coronary syndrome or in patients with heart failure. Further studies will advance our understanding of the link between β2-AR genotypes, intermediate cardiovascular phenotypes, and clinical phenotypes. In the long term, reassessment of the benefits of β-blocker-therapy within genotype groups should be carried out with the ultimate goal to design the optimal therapeutic regimen for the individual patient.

KW - β-adrenergic receptor

KW - Genotype

KW - Haplotype

KW - Phenotype

KW - Polymorphism

UR - http://www.scopus.com/inward/record.url?scp=67649445926&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67649445926&partnerID=8YFLogxK

M3 - Article

VL - 6

SP - 160

EP - 170

JO - Current Pharmacogenomics and Personalized Medicine

JF - Current Pharmacogenomics and Personalized Medicine

SN - 1875-6921

IS - 3

ER -