Evidence map›Paper›PMID 18425130›Full record

ArticleNature medicine2008

A GRK5 polymorphism that inhibits beta-adrenergic receptor signaling is protective in heart failure.

Stephen B Liggett, Sharon Cresci, Reagan J Kelly, Faisal M Syed, Scot J Matkovich, Harvey S Hahn, Abhinav Diwan, Jeffrey S Martini, Li Sparks, Rohan R Parekh and 4 more

Open access · greenAbstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature medicine, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 163 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
163citing papers in PubMed, 1 pooled it
15.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

163 citing papers in PubMed, 1 synthesis or guideline pooled it, 320 citations in OpenAlex.

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  17. Molecular Mechanisms of Takotsubo Syndrome.International journal of molecular sciences · 2022
    Review
  18. G protein-coupled receptor signaling: transducers and effectors.American journal of physiology. Cell physiology · 2022
    Review
  19. Article
  20. Review

103 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 6 institutions in 1 country.

Stephen B LiggettDepartment of Internal Medicine, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, Ohio 45267, USA.
Sharon Cresci
Reagan J Kelly
Faisal M Syed
Scot J Matkovich
Harvey S Hahn
Abhinav Diwan
Jeffrey S Martini
Li Sparks
Rohan R Parekh
John A Spertus
Walter J Koch
Sharon L R Kardia
Gerald W Dorn
Sabin Vaccine Institute · USUniversity of Cincinnati · USThomas Jefferson University · USUniversity of Michigan–Ann Arbor · USWashington University in St. Louis · USUniversity of Missouri–Kansas City · US

Funding

PKCa Signaling Regulates Contractility and Heart FailureP50HL077101 · NHLBI · UNIVERSITY OF CINCINNATI · PI MOLKENTIN, JEFFERY D · 2005 to 2009
$19.1M
SCCOR in Cardiac Dysfunction and DiseaseP50HL077113 · NHLBI · WASHINGTON UNIVERSITY · PI KELLY, DANIEL PATRICK · 2005 to 2009
$13.4M
G-Protein Receptor Kinases in Cardiac Stress AdaptationR01HL087871 · NHLBI · WASHINGTON UNIVERSITY · PI DORN, GERALD W. · 2007 to 2016
$4.1M
NHLBI NIH HHS HL77113NHLBI NIH HHS P50 HL077101NHLBI NIH HHS P50 HL077113NHLBI NIH HHS P50 HL77101NHLBI NIH HHS R01 HL087871NHLBI NIH HHS R01 HL87871
6 · The paper itself

Abstract

Beta-adrenergic receptor (betaAR) blockade is a standard therapy for cardiac failure and ischemia. G protein-coupled receptor kinases (GRKs) desensitize betaARs, suggesting that genetic GRK variants might modify outcomes in these syndromes. Re-sequencing of GRK2 and GRK5 revealed a nonsynonymous polymorphism of GRK5, common in African Americans, in which leucine is substituted for glutamine at position 41. GRK5-Leu41 uncoupled isoproterenol-stimulated responses more effectively than did GRK5-Gln41 in transfected cells and transgenic mice, and, like pharmacological betaAR blockade, GRK5-Leu41 protected against experimental catecholamine-induced cardiomyopathy. Human association studies showed a pharmacogenomic interaction between GRK5-Leu41 and beta-blocker treatment, in which the presence of the GRK5-Leu41 polymorphism was associated with decreased mortality in African Americans with heart failure or cardiac ischemia. In 375 prospectively followed African-American subjects with heart failure, GRK5-Leu41 protected against death or cardiac transplantation. Enhanced betaAR desensitization of excessive catecholamine signaling by GRK5-Leu41 provides a 'genetic beta-blockade' that improves survival in African Americans with heart failure, suggesting a reason for conflicting results of beta-blocker clinical trials in this population.

Indexed as

Adrenergic beta-AntagonistsAnimalsBase SequenceBlack or African AmericanCHO CellsCricetinaeCricetulusGene FrequencyG-Protein-Coupled Receptor Kinase 5Heart FailureHumansMiceMice, TransgenicMolecular Sequence DataPharmacogeneticsPolymorphism, Single NucleotideAdrenergic beta-AntagonistsG-Protein-Coupled Receptor Kinase 5GRK5 protein, humanReceptors, Adrenergic, beta

Identifiers

PMID18425130
PMCPMC2596476
OpenAlexW2070551632

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.