Association of Common Polymorphisms in β1-adrenergic Receptor With Antihypertensive Response to Carvedilol

Si, Daoyuan; Wang, Juan; Xü, Ying; Chen, Xiaoshuai; Zhang, Mingqiu; Zhou, Hui

doi:10.1097/fjc.0000000000000119

Cited by 23 publications

(14 citation statements)

References 30 publications

(27 reference statements)

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“…The gene ADRB1 codes for the β1 receptor, and two SNPs within this gene were originally identified in population studies as a risk factor for HTN [50]. The A allele at rs1801252 leads to a Ser49 variant, which leads to increased receptor internalization, while the C allele at associated with significantly better blood pressure response to beta blockers [51][52][53][54]. Importantly, analysis of the INVEST trial found that participants with the Ser49/Arg389 haplotype was associated with higher mortality when treated with a verapamil based strategy, as opposed to a beta blockers [55].…”

Section: Beta Blockersmentioning

confidence: 99%

Pharmacogenomics in Hypertension: Where We Stand Today

Cunningham¹,

Chapman²

2019

Preprint

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Hypertension is a common and growing medical problem that leads to enormous cardiovascular and kidney disease worldwide. While many drugs exist to treat hypertension, there is large individual variation in how a given individual responds to different agents, which contributes to dismal rates of hypertension control. While demographic factors predict which drugs may work better in certain individuals, a great degree of this variation has a genetic basis. In recent years, genome wide association studies have begun to identify specific gene variants that predict drug response to particular agents. This review identifies the major genetic variants influencing antihypertensive response that have emerged from this growing body of work. For novel genetic variants without a previously known biologic basis in blood pressure, it is crucial to validate initial findings in subsequent studies. This information may eventually lead to a more personalized approach to hypertension management that will improve blood pressure control and patient outcomes. The integration of this large amount of data and its real world application will be highly challenging, but strategies to accomplish this are discussed.

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Section: Beta Blockersmentioning

confidence: 99%

Pharmacogenomics in Hypertension: Where We Stand Today

Cunningham¹,

Chapman²

2019

Preprint

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“…Another GWAS study in over 60,000 subjects identified a polymorphism of ADRB1 associated with hypertension and the response to β-blockers. This gene encodes the β-1 adrenergic receptor for the catecholamines, and the Arg389 and Ser49/Arg389 haplotypes have been associated with greater response to β-blockers [ 114 – 117 ]. Interestingly, in the INVEST study, patients with these aplotypes presented increased cardiovascular risk on verapamil therapy alone, the risk was offset by using β-blockers.…”

Section: Integrative ‘Omics’ As Predictive Diagnostic and Prognostimentioning

confidence: 99%

Personalized medicine—a modern approach for the diagnosis and management of hypertension

et al. 2017

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The main goal of treating hypertension is to reduce blood pressure to physiological levels and thereby prevent risk of cardiovascular disease and hypertension-associated target organ damage. Despite reductions in major risk factors and the availability of a plethora of effective antihypertensive drugs, the control of blood pressure to target values is still poor due to multiple factors including apparent drug resistance and lack of adherence. An explanation for this problem is related to the current reductionist and ‘trial-and-error’ approach in the management of hypertension, as we may oversimplify the complex nature of the disease and not pay enough attention to the heterogeneity of the pathophysiology and clinical presentation of the disorder. Taking into account specific risk factors, genetic phenotype, pharmacokinetic characteristics, and other particular features unique to each patient, would allow a personalized approach to managing the disease. Personalized medicine therefore represents the tailoring of medical approach and treatment to the individual characteristics of each patient and is expected to become the paradigm of future healthcare. The advancement of systems biology research and the rapid development of high-throughput technologies, as well as the characterization of different –omics, have contributed to a shift in modern biological and medical research from traditional hypothesis-driven designs toward data-driven studies and have facilitated the evolution of personalized or precision medicine for chronic diseases such as hypertension.

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“…Indeed a number of studies 46–49 , although not all 50,51 , have shown that the Arg389 allele, particularly the Arg389Arg genotype or the Ser49/Arg389 haplotype, is associated with greater blood pressure lowering in response to β-blockers than are other variants. In one study, individuals who were homozygous for the Arg389 allele had a greater blood pressure response to the β-blocker metoprolol (with a difference in 24 h DBP of −6.5 mmHg compared to carriers of the Gly389 allele, P = 0.0018) 46 .…”

Section: Hypertension Pharmacogenomicsmentioning

confidence: 99%

Hypertension pharmacogenomics: in search of personalized treatment approaches

Cooper‐DeHoff

Johnson

2015

Nat Rev Nephrol

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Cardiovascular and renal diseases are associated with many risk factors, of which hypertension is one of the most prevalent. Worldwide, blood pressure control is only achieved in ~50% of those treated for hypertension, despite the availability of a considerable number of antihypertensive drugs from different pharmacological classes. Although many reasons exist for poor blood pressure control, a likely contributor is the inability to predict to which antihypertensive drug an individual is most likely to respond. Hypertension pharmacogenomics and other ‘omics’ technologies have the potential to identify genetic signals that are predictive of response or adverse outcome to particular drugs, and guide selection of hypertension treatment for a given individual. Continued research in this field will enhance our understanding of how to maximally deploy the various antihypertensive drug classes to optimize blood pressure response at the individual level. This Review summarizes the available literature on the most convincing genetic signals associated with antihypertensive drug responses and adverse cardiovascular outcomes. Future research in this area will be facilitated by enhancing collaboration between research groups through consortia such as the International Consortium for Antihypertensives Pharmacogenomics Studies, with the goal of translating replicated findings into clinical implementation.

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Association of Common Polymorphisms in β1-adrenergic Receptor With Antihypertensive Response to Carvedilol

Abstract: This study provides the first evidence to support that ADRB1 polymorphisms play an important role in the DBPs response to carvedilol treatment in patients with essential hypertension.

Cited by 23 publications

References 30 publications

Pharmacogenomics in Hypertension: Where We Stand Today

Pharmacogenomics in Hypertension: Where We Stand Today

Personalized medicine—a modern approach for the diagnosis and management of hypertension

Hypertension pharmacogenomics: in search of personalized treatment approaches

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