ArticlePharmacogenetics and genomics2011
Polymorphisms in genes coding for GRK2 and GRK5 and response differences in antihypertensive-treated patients.
Article in Pharmacogenetics and genomics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00246519 (Pharmacogenomic Evaluation of Antihypertensive Responses), which is not on this map. Cited by 38 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR)
Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Why do hypertensive patients of African ancestry respond better to calcium blockers and diuretics than to ACE inhibitors and β-adrenergic blockers? A systematic review.BMC medicine · 2013Pooled it
- The effects of genes implicated in cardiovascular disease on blood pressure response to treatment among treatment-naive hypertensive African Americans in the GenHAT study.Journal of human hypertension · 2016Trial
- TET2 and CSMD1 genes affect SBP response to hydrochlorothiazide in never-treated essential hypertensives.Journal of hypertension · 2015Trial
- Article
- Revealing GRK5 Activation Features by Interpretable Machine Learning and Molecular Dynamics Simulation.International journal of molecular sciences · 2026Article
- Blood indices of inflammation and their association with hypertension in smokers: analysis using data mining approaches.Journal of human hypertension · 2025Article
- Effect of Clinical and Genetic Factors on the Development of Postoperative Atrial Fibrillation After Coronary Artery Bypass Grafting (CABG) in Egyptian Patients Receiving Beta-Blockers.Cardiovascular drugs and therapy · 2024Article
- Comprehensive insights in GRK4 and hypertension: From mechanisms to potential therapeutics.Pharmacology & therapeutics · 2022Review
- Pharmacogenetics to guide cardiovascular drug therapy.Nature reviews. Cardiology · 2021Review
- Pharmacogenetic factors affecting β-blocker metabolism and response.Expert opinion on drug metabolism & toxicology · 2020Review
- The Roles of GRKs in Hemostasis and Thrombosis.International journal of molecular sciences · 2020Review
- G protein-coupled receptor kinase 2 (GRK2) as a multifunctional signaling hub.Cellular and molecular life sciences : CMLS · 2019Review
- The relationship between red blood cell distribution width and metabolic syndrome in elderly Chinese: a cross-sectional study.Lipids in health and disease · 2019Article
- Association of hematocrit with blood pressure and hypertension.Journal of clinical laboratory analysis · 2017Article
- The influence of two functional genetic variants of GRK5 on tau phosphorylation and their association with Alzheimer's disease risk.Oncotarget · 2017Article
- Secreted miR-27a Induced by Cyclic Stretch Modulates the Proliferation of Endothelial Cells in Hypertension via GRK6.Scientific reports · 2017Article
- The analysis of heterotaxy patients reveals new loss-of-function variants of GRK5.Scientific reports · 2016Article
- Association Between Polymorphisms of ADRBK1 Gene and Plasma Renin Activity in Hypertensive Patients: A Case-Control Study.Medical science monitor : international medical journal of experimental and clinical research · 2016Article
- G Protein-Coupled Receptor Kinases: Crucial Regulators of Blood Pressure.Journal of the American Heart Association · 2016Review
- Prehypertension in adolescents with cardiovascular risk: a comparison between type 1 diabetic patients and overweight subjects.BMC research notes · 2016Observational
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 6 institutions in 1 country.
Funding
Abstract
objectivesThe G-protein-coupled receptor kinases (GRKs) GRK2 and GRK5 are important regulators of β-adrenergic signaling. This study characterized single-nucleotide polymorphisms (SNPs) in the GRK2 gene (ADRBK1) and determined if these and a GRK5 Gln41Leu polymorphism affect the blood pressure (BP) response to atenolol or hydrochlorothiazide or adverse cardiovascular outcomes in hypertensives.
methodsADRBK1 regions were sequenced for 48 individuals. Putative functional SNPs were tested for mRNA expression differences in 96 lymphoblastoid cell line samples and 12 leukocyte samples from hypertensives. BP response to atenolol and hydrochlorothiazide by ADRBK1 SNPs and GRK5 Gln41Leu was tested in 418 patients from the Pharmacogenomic Evaluation of Antihypertensive Responses Study using linear regression. The influence of ADRBK1 SNPs and GRK5 Gln41Leu on death, myocardial infarction or stroke in treated hypertensives was evaluated in a case-control cohort (1 : 3) of the International Verapamil SR/Trandolapril Study GENEtic Substudy using logistic regression models.
resultsA novel ADRBK1 promoter SNP was not associated with differential GRK2 expression. GRK5 Leu41 decreased the risk for adverse cardiovascular outcomes independent of treatment strategy (adjusted odds ratio 0.535, 95% confidence interval: 0.313-0.951, P=0.0222), but was not associated with BP response to antihypertensive medication. An ADRBK1 SNP (rs1894111 G>A) showed a signal for association with systolic and diastolic BP response to hydrochlorothiazide in Whites [diastolic BP: -11.29±3.74 (G/A) versus -4.26±4.79 mmHg (G/G), P=0.0034 and systolic BP: -18.37±14.90 (G/A), -8.11±7.55 mmHg (G/G), P=0.0191].
conclusionThe GRK5 Leu41 allele protects from adverse cardiovascular outcomes in treated hypertensives.
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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.