ArticleBlood2014
Common variants in the human platelet PAR4 thrombin receptor alter platelet function and differ by race.
Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05709483 (Genetic, Laboratory and Clinical Factors Associated With Low-dose Aspirin Failure in the Prevention of Preeclampsia- An Exploratory Protocol), which is not on this map. Cited by 68 papers.
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, Laboratory and Clinical Factors Associated With Low-dose Aspirin Failure in the Prevention of Preeclampsia- An Exploratory Protocol
Who cites it
68 citing papers in PubMed, 130 citations in OpenAlex.
- Effects of genetic variation in protease activated receptor 4 after an acute coronary syndrome: Analysis from the TRACER trial.Blood cells, molecules & diseases · 2018Trial
- To generate functional anti-protease-activated receptor-4 (PAR4), a G protein-coupled receptor, antibodies through PAR4-mRNA-LNP immunization.NPJ vaccines · 2025Article
- Humanized murine models of platelet function.Current opinion in hematology · 2025Review
- Platelet protease-activated receptor 4 genotype and response to aspirin in pregnancy.Blood vessels, thrombosis & hemostasis · 2025Article
- Scoring systems to predict thrombotic complications in solid tumor patients.Current opinion in hematology · 2025Review
- Mice with reduced protease-activated receptor 4 reactivity show decreased venous thrombosis and platelet procoagulant activity.Journal of thrombosis and haemostasis : JTH · 2025Article
- Endothelial protease-activated receptor 4: impotent or important?Frontiers in cardiovascular medicine · 2025Review
- Demographic diversity in platelet function and response to antiplatelet therapy.Trends in pharmacological sciences · 2025Review
- Observational Analyses of Ex Vivo Native American Platelet Responses.International journal of molecular sciences · 2024Observational
- Mice with Reduced PAR4 Reactivity show Decreased Venous Thrombosis and Platelet Procoagulant Activity.bioRxiv : the preprint server for biology · 2024Article
- A mouse model of the protease-activated receptor 4 Pro310Leu variant has reduced platelet reactivity.Journal of thrombosis and haemostasis : JTH · 2024Article
- Ethnic Disparities in the Risk Factors, Morbidity, and Mortality of Cardiovascular Disease in People With Diabetes.Journal of the Endocrine Society · 2024Review
- Association of laboratory test results with the bleeding history in patients with inherited platelet function disorders (the Bleeding Assesment Tool - LABoratory tests substudy): communication from the Platelet Physiology ISTH-SSC.Research and practice in thrombosis and haemostasis · 2024Article
- Targeting PAR4 to Reduce Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
- Identification of genomic loci regulating platelet plasminogen activator inhibitor-1 in mice.Journal of thrombosis and haemostasis : JTH · 2023Article
- Mouse model hints at pharmacogenomic strategies for stroke treatment in patients possessing a risk variant.The Journal of clinical investigation · 2023Article
- The predominant PAR4 variant in individuals of African ancestry worsens murine and human stroke outcomes.The Journal of clinical investigation · 2023Article
- Species Differences in Platelet Protease-Activated Receptors.International journal of molecular sciences · 2023Review
- Review of Cardiovascular Risk of Androgen Deprivation Therapy and the Influence of Race in Men with Prostate Cancer.Cancers · 2023Review
- A comprehensive review of the ten main platelet receptors involved in platelet activity and cardiovascular disease.American journal of blood research · 2023Review
8 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
13 authors at 3 institutions in 1 country.
Funding
Abstract
Human platelets express 2 thrombin receptors: protease-activated receptor (PAR)-1 and PAR4. Recently, we reported 3.7-fold increased PAR4-mediated aggregation kinetics in platelets from black subjects compared with white subjects. We now show that platelets from blacks (n = 70) express 14% more PAR4 protein than those from whites (n = 84), but this difference is not associated with platelet PAR4 function. Quantitative trait locus analysis identified 3 common single nucleotide polymorphisms in the PAR4 gene (F2RL3) associated with PAR4-induced platelet aggregation. Among these single nucleotide polymorphisms, rs773902 determines whether residue 120 in transmembrane domain 2 is an alanine (Ala) or threonine (Thr). Compared with the Ala120 variant, Thr120 was more common in black subjects than in white subjects (63% vs 19%), was associated with higher PAR4-induced human platelet aggregation and Ca2+ flux, and generated greater inositol 1,4,5-triphosphate in transfected cells. A second, less frequent F2RL3 variant, Phe296Val, was only observed in blacks and abolished the enhanced PAR4-induced platelet aggregation and 1,4,5-triphosphate generation associated with PAR4-Thr120. PAR4 genotype did not affect vorapaxar inhibition of platelet PAR1 function, but a strong pharmacogenetic effect was observed with the PAR4-specific antagonist YD-3 [1-benzyl-3(ethoxycarbonylphenyl)-indazole]. These findings may have an important pharmacogenetic effect on the development of new PAR antagonists.
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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.