Polymorphisms of the β1-adrenergic receptor predict exercise capacity in heart failure

Wagoner, Lynne E.; Craft, L.; Zengel, Paul W.; McGuire, Nancy; Rathzb, Deborah A.; Dorn, Gerald W.; Liggett, Stephen B.

doi:10.1067/mhj.2002.125325

Cited by 119 publications

(58 citation statements)

References 26 publications

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“…Exercise-induced increase in heart rate appeared to be unaffected by the Arg389Gly polymorphism (Buscher et al, 2001;Xie et al, 2001) in healthy volunteers. In contrast, heart failure patients homozygous for the Gly389 polymorphism had depressed exercise performance compared to those with Arg389-b 1 -adrenoceptors (Wagoner et al, 2002). The positive inotropic effects of noradrenaline on robust trabeculae from human atria, usually from nonfailing hearts of patients with coronary heart disease, were not affected by the Arg389Gly polymorphism (Molenaar et al, 2002), but were enhanced in weak trabeculae from Arg389 patients compared to weak atrial trabeculae from Gly389 patients (Sandilands et al, 2003).…”

Section: Introductionmentioning

confidence: 91%

Markedly reduced effects of (−)‐isoprenaline but not of (−)‐CGP12177 and unchanged affinity of β‐blockers at Gly389‐β₁‐adrenoceptors compared to Arg389‐β₁‐adrenoceptors

Joseph

Lynham

Grace

et al. 2004

British J Pharmacology

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Section: Introductionmentioning

confidence: 91%

Markedly reduced effects of (−)‐isoprenaline but not of (−)‐CGP12177 and unchanged affinity of β‐blockers at Gly389‐β₁‐adrenoceptors compared to Arg389‐β₁‐adrenoceptors

Joseph

Lynham

Grace

et al. 2004

British J Pharmacology

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“…Another study found impaired exercise capacity in patients with ischemic or dilated cardiomyopathy homozygous for the Ser49 allele compared to Gly49 carriers. 87 In contrast, Podlowski and colleagues 86 only found the Gly49 mutation in patients with idiopathic dilated cardiomyopathy and not in healthy volunteers.…”

Section: ␤ 1 -Adrenergic Receptor Polymorphismsmentioning

confidence: 99%

“…An impaired exercise performance was demonstrated in patients with ischemic or idiopathic dilated cardiomyopathy, who were homozygous for Gly389 compared to Arg389 homozygotes, with an intermediate level of performance in heterozygotes. 87 This may suggest a role for the Arg389Gly polymorphism as a disease modifier. Also, a study in patients with renal disease found higher cardiac mass in Gly389 homozygotes.…”

Section: ␤ 1 -Adrenergic Receptor Polymorphismsmentioning

confidence: 99%

Genetic polymorphisms and heart failure

Bleumink

Schut

Sturkenboom

et al. 2004

Genetics in Medicine

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Heart failure is a complex clinical syndrome. There is evidence for a genetic contribution to the pathophysiology of heart failure. Considering the fundamental role of neurohormonal factors in the pathophysiology and progression of cardiac dysfunction and hypertrophy, variants of genes involved in this system are logical candidate genes in heart failure. In this report, genetic polymorphisms of the major neurohormonal systems in heart failure will be discussed. Studies on polymorphisms of the renin-angiotensin-aldosterone system (RAAS), adrenergic receptor polymorphisms, endothelin (receptor) polymorphisms, and a group of miscellaneous polymorphisms that may be involved in the development or phenotypic expression of heart failure will be reviewed. Research on left ventricular hypertrophy is also included. The majority of genetic association studies focused on the ACE I/D polymorphism.Initial genetic associations have often been difficult to replicate, mainly due to problems in study design and lack of power. Promising results have been obtained with genetic polymorphisms of the RAAS and sympathetic system.Considering the evidence so far, a modifying role for these polymorphisms seems more likely than a role of these variants as susceptibility genes. Besides the need for larger studies to examine the effects of single nucleotide polymorphisms and haplotypes, future studies also need to focus on the complexity of these systems and study Heart failure is a complex clinical syndrome with high morbidity and mortality. 1,2 Impairment of cardiac function activates compensatory neurohormonal mechanisms, which at a later stage may accelerate progression of heart failure. 3 Coronary heart disease and hypertension are major underlying causes of heart failure. Other frequent underlying conditions include valvular heart disease and idiopathic dilated cardiomyopathy. It is difficult to predict who will develop heart failure in response to myocardial injury. Racial differences in occurrence and outcome of heart failure 4,5 and heritability estimates of variability in left ventricular mass of 28% to 65% 6,7 suggest a genetic contribution to the pathophysiology of left ventricular remodeling and heart failure.Many studies have been published on the role of single gene mutations in (familial) cardiomyopathies. 8,9 These Mendelian traits are by nature rare, and although important at an individual level and for the understanding of disease mechanisms, are of limited significance in terms of prediction of heart failure occurrence in the population. 10 Moreover, in patients with identical gene mutations clinical manifestations of cardiomyopathy may differ. This suggests that probably also environmental and/or other genetic factors play a role.In this report, genetic polymorphisms of major neurohormonal systems involved in the pathophysiology of heart failure will be discussed, including the renin-angiotensin-aldosterone system (RAAS), adrenergic receptor polymorphisms, endothelin (receptor) polymorphisms, and a group of miscellaneous...

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“…[4][5][6][7][8] SNPs in the β 1 -adrenergic receptor may not affect clinical outcome in HF, 4,5 whereas softer end points were shown to be associated with certain genotypes. 6 Possibly, other SNPs modulate their impact of a single SNP. 7 SNPs in the gene encoding the β 2 -adrenergic receptor have convincingly been associated with adverse outcomes in HF.…”

Section: Genetics In Hf: Where Are We Now?mentioning

confidence: 99%

Genetics in Heart Failure: Where Are We Headed?

Boer

Berg

Veldhuisen

2006

Congestive Heart Failure

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Heart failure is a complex disease with many precipitating factors. Novel insights into the genetic background of heart failure have boosted new areas of research that gave rise to the concept of genetic predisposition for heart failure. Various genetic defects and variances have been identified and subsequently linked to the onset of or progression to heart failure. Nevertheless, our understanding of the genetic basis for heart failure is incomplete because we lack knowledge of the functionality of genetic variances. We also do not understand the impact of genetic variances in noncoding DNA because of logistic problems in performing whole‐genome scans and difficulties in statistical evaluation of large amounts of data generated by the genetic boom. It is expected that in the future we will be able to overcome these problems and apply the knowledge gained by genetic analyses to target and optimize treatment.

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Polymorphisms of the β1-adrenergic receptor predict exercise capacity in heart failure

Cited by 119 publications

References 26 publications

Markedly reduced effects of (−)‐isoprenaline but not of (−)‐CGP12177 and unchanged affinity of β‐blockers at Gly389‐β₁‐adrenoceptors compared to Arg389‐β₁‐adrenoceptors

Markedly reduced effects of (−)‐isoprenaline but not of (−)‐CGP12177 and unchanged affinity of β‐blockers at Gly389‐β₁‐adrenoceptors compared to Arg389‐β₁‐adrenoceptors

Genetic polymorphisms and heart failure

Genetics in Heart Failure: Where Are We Headed?

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Polymorphisms of the β1-adrenergic receptor predict exercise capacity in heart failure

Cited by 119 publications

References 26 publications

Markedly reduced effects of (−)‐isoprenaline but not of (−)‐CGP12177 and unchanged affinity of β‐blockers at Gly389‐β1‐adrenoceptors compared to Arg389‐β1‐adrenoceptors

Markedly reduced effects of (−)‐isoprenaline but not of (−)‐CGP12177 and unchanged affinity of β‐blockers at Gly389‐β1‐adrenoceptors compared to Arg389‐β1‐adrenoceptors

Genetic polymorphisms and heart failure

Genetics in Heart Failure: Where Are We Headed?

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Resources

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Markedly reduced effects of (−)‐isoprenaline but not of (−)‐CGP12177 and unchanged affinity of β‐blockers at Gly389‐β₁‐adrenoceptors compared to Arg389‐β₁‐adrenoceptors

Markedly reduced effects of (−)‐isoprenaline but not of (−)‐CGP12177 and unchanged affinity of β‐blockers at Gly389‐β₁‐adrenoceptors compared to Arg389‐β₁‐adrenoceptors