ArticleThe Journal of clinical investigation1998
The Ile164 beta2-adrenergic receptor polymorphism adversely affects the outcome of congestive heart failure.
Article in The Journal of clinical investigation, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
63 citing papers in PubMed, 340 citations in OpenAlex.
- Impact of beta2-adrenoreceptor gene variants on cardiac cavity size and systolic function in idiopathic dilated cardiomyopathy.The pharmacogenomics journal · 2007Trial
- Carvedilol improves left ventricular function in heart failure patients with idiopathic dilated cardiomyopathy and a wide range of sympathetic nervous system function as measured by iodine 123 metaiodobenzylguanidine.Journal of nuclear cardiology : official publication of the American Society of Nuclear CardiologyTrial
- Review
- The progress and controversial of the use of beta blockers in patients with heart failure with a preserved ejection fraction.International journal of cardiology. Heart & vasculature · 2020Review
- Anabolic Hormones Deficiencies in Heart Failure With Preserved Ejection Fraction: Prevalence and Impact on Antioxidants Levels and Myocardial Dysfunction.Frontiers in endocrinology · 2020Article
- ADRB2 polymorphism Arg16Gly modifies the natural outcome of heart failure and dictates therapeutic response to β-blockers in patients with heart failure.Cell discovery · 2018Article
- Induced Pluripotent Stem Cell-Derived Cardiomyocytes: A Platform for Testing For Drug Cardiotoxicity.Progress in pediatric cardiology · 2017Article
- Raf kinase inhibitor protein: lessons of a better way for β-adrenergic receptor activation in the heart.The Journal of physiology · 2017Review
- Practical Pharmacogenomic Approaches to Heart Failure Therapeutics.Current treatment options in cardiovascular medicine · 2016Review
- Genetic polymorphisms associated with heart failure: A literature review.The Journal of international medical research · 2016Review
- Biased β2-adrenoceptor signalling in heart failure: pathophysiology and drug discovery.British journal of pharmacology · 2015Review
- Determined to Fail--the Role of Genetic Mechanisms in Heart Failure.Current heart failure reports · 2015Review
- Genetics and heart failure: a concise guide for the clinician.Current cardiology reviews · 2015Review
- Effect of rare variants in ADRB2 on risk of severe exacerbations and symptom control during longacting β agonist treatment in a multiethnic asthma population: a genetic study.The Lancet. Respiratory medicine · 2014Article
- Genetic prediction of heart failure incidence, prognosis and beta-blocker response.Molecular diagnosis & therapy · 2013Review
- Genetic mutations and mechanisms in dilated cardiomyopathy.The Journal of clinical investigation · 2013Review
- Genetics of asthma susceptibility and severity.Clinics in chest medicine · 2012Review
- Pharmacogenetics in chronic heart failure: new developments and current challenges.Current heart failure reports · 2012Review
- Genetic variation, β-blockers, and perioperative myocardial infarction.Anesthesiology · 2011Review
- Principal role of adenylyl cyclase 6 in K⁺ channel regulation and vasodilator signalling in vascular smooth muscle cells.Cardiovascular research · 2011Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The beta2-adrenergic receptor (beta2AR), an important modulator of cardiac inotropy and chronotropy, has significant genetic heterogeneity in the population. Because dysfunctional betaARs play a role in the pathogenesis of the failing ventricle, we tested the hypothesis that beta2AR polymorphisms alter the outcome of congestive heart failure. 259 patients with NYHA functional class II-IV heart failure due to ischemic or dilated cardiomyopathy were genotyped and prospectively followed, with the endpoint defined as death or cardiac transplantation. The allele frequencies between this group and those of 212 healthy controls also were compared and did not differ between the groups. However, those with the Ile164 polymorphism displayed a striking difference in survival with a relative risk of death or cardiac transplant of 4.81 (P < 0.001) compared with those with the wild-type Thr at this position. Age, race, gender, functional class, etiology, ejection fraction, and medication use did not differ between these individuals and those with the wild-type beta2AR, and thus the beta2AR genotype at position 164 was the only clear distinguishing feature between the two groups. The 1-yr survival for Ile164 patients was 42% compared with 76% for patients harboring wild-type beta2AR. In contrast, polymorphisms at amino acid positions 16 (Arg or Gly) or 27 (Gln or Glu), which also alter receptor phenotype, did not appear to have an influence on the course of heart failure. Taken together with cell-based and transgenic mouse results, this study establishes a paradigm whereby genetic variants of key signaling elements can have pathophysiologic consequences within the context of a disease. Furthermore, patients with the Ile164 polymorphism and heart failure may be candidates for earlier aggressive intervention or cardiac transplantation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.