ArticlePharmacogenomics2009
GRK5 Gln41Leu polymorphism is not associated with sensitivity to beta(1)-adrenergic blockade in humans.
Article in Pharmacogenomics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00837902 (Genetic Determinants of Response to Beta Blockade), which is not on this map. Cited by 14 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.
Genetic Determinants of Response to Beta Blockade
Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 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
- A narrative review of research advancements in pharmacogenetics of cardiovascular disease and impact on clinical implications.NPJ genomic medicine · 2025Review
- Impact of Genetic Variation in Adrenergic Receptors on β-Blocker Effectiveness and Safety in Cardiovascular Disease Management: A Systematic Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Sex/Gender- and Age-Related Differences in β-Adrenergic Receptor Signaling in Cardiovascular Diseases.Journal of clinical medicine · 2022Review
- The genetics of cardiac failure: Role of a G protein-coupled receptor polymorphism in therapeutic response in an Indian population.Journal of clinical and translational research · 2021Article
- Pharmacogenetic factors affecting β-blocker metabolism and response.Expert opinion on drug metabolism & toxicology · 2020Review
- Genetics of heart rate in heart failure patients (GenHRate).Human genomics · 2019Article
- "Canonical and non-canonical actions of GRK5 in the heart".Journal of molecular and cellular cardiology · 2016Review
- Genetic variation in alpha2-adrenoreceptors and heart rate recovery after exercise.Physiological genomics · 2015Article
- Effects of GRK5 and ADRB1 polymorphisms influence on systolic heart failure.Journal of translational medicine · 2015Article
- A case for pharmacogenomics in management of cardiac arrhythmias.Indian pacing and electrophysiology journal · 2012Article
- Article
- Genetic variation in the presynaptic norepinephrine transporter is associated with blood pressure responses to exercise in healthy humans.Pharmacogenetics and genomics · 2011Article
- Polymorphisms in genes coding for GRK2 and GRK5 and response differences in antihypertensive-treated patients.Pharmacogenetics and genomics · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
aimsA common, functionally significant polymorphism in GRK5 (Gln41Leu) encodes a gain-of-function enzyme that enhances desensitization of the beta(1)-adrenergic receptor. GRK5 Leu41 has been postulated to confer endogenous 'genetic beta-blockade' and contribute to an attenuated response to beta-blockers in black subjects. The effects of this GRK5 variant on sensitivity to a beta-blocker have not been studied in humans. We hypothesized that the GRK5 Gln41Leu variant contributes to interindividual variability in response to beta-blockade and to the ethnic difference in sensitivity between black and Caucasian individuals. MATERIALS &
methodsWe measured the heart rate at rest and during a graded incremental exercise in 154 healthy subjects (85 white and 69 black) before and after an oral administration of 25 mg atenolol. We determined the genotypes of GRK5 (Gln41Leu), beta(1)-adrenergic receptor (ADRB1 Ser49Gly and Arg389Gly) genotypes and plasma atenolol concentrations. The effects of genotype and covariates on sensitivity to atenolol, measured as the reduction in exercise-induced tachycardia, were determined using multiple regression analyses.
resultsThe minor allele frequency of GRK5 Leu41 was 32.6% in blacks and 0% in whites. Black individuals were less sensitive to atenolol than white individuals (p < or = 0.011) but this was not explained by the GRK5 genotype. The GRK5 genotype had no effect on resting heart rate before (p = 0.61) and after adjustment for age, sex, ethnicity, atenolol concentrations, BMI and ADRB1 genotypes (p = 0.81). The decrease in heart rate after atenolol administration did not differ significantly according to the GRK5 genotype at rest or after exercise, before (all p > 0.14) and after statistical adjustment for covariates (all p > 0.17).
conclusionThe GRK5 Gln41Leu polymorphism does not affect sensitivity to the beta(1)-adrenergic blocker, atenolol, during acute physiological adrenergic stimulation, nor does it contribute to the ethnic differences in sensitivity to atenolol among black and Caucasian individuals.
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Registered trials
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