ArticleBlood2019
The von Willebrand factor Tyr2561 allele is a gain-of-function variant and a risk factor for early myocardial infarction.
Article in Blood, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- Assessing genetic risk factors for early-onset coronary artery disease in Iranians.Research and practice in thrombosis and haemostasis · 2026Article
- Identification of missense variants in the C-domains of von Willebrand factor that cause gain-of-function-like activity.Blood advances · 2026Article
- The pivotal role of von Willebrand factor binding to platelet αIIbβ3 in stabilizing the formation of a platelet plug at sites of injury.Haematologica · 2025Article
- An Exploratory Study Using Next-Generation Sequencing to Identify Prothrombotic Variants in Patients with Cerebral Vein Thrombosis.International journal of molecular sciences · 2023Article
- The intestinal MUC2 mucin C-terminus is stabilized by an extra disulfide bond in comparison to von Willebrand factor and other gel-forming mucins.Nature communications · 2023Article
- Type 2B von Willebrand disease mutations differentially perturb autoinhibition of the A1 domain.Blood · 2023Article
- From multi-omics approaches to personalized medicine in myocardial infarction.Frontiers in cardiovascular medicine · 2023Review
- Gain-of-Function Variant p.Pro2555Arg of von Willebrand Factor Increases Aggregate Size through Altering Stem Dynamics.Thrombosis and haemostasis · 2022Article
- Review
- DNA binds to a specific site of the adhesive blood-protein von Willebrand factor guided by electrostatic interactions.Nucleic acids research · 2020Article
- Impact of Von Willebrand Factor on Bacterial Pathogenesis.Frontiers in medicine · 2020Review
- Effect of Acute Myocardial Infarction on a Disintegrin and Metalloprotease with Thrombospondin Motif 13 and Von Willebrand Factor and Their Relationship with Markers of Inflammation.International journal of vascular medicine · 2020Article
- Article
- Domain-specific mechanical modulation of VWF-ADAMTS13 interaction.Molecular biology of the cell · 2019Article
- Structure and dynamics of the platelet integrin-binding C4 domain of von Willebrand factor.Blood · 2019Article
- Genetic and Clinical Predictors of Left Atrial Thrombus: A Single Center Case-Control Study.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/HemostasisArticle
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Authors and funding
14 authors at 7 institutions in 4 countries.
Funding
Abstract
The frequent von Willebrand factor (VWF) variant p.Phe2561Tyr is located within the C4 domain, which also harbors the platelet GPIIb/IIIa-binding RGD sequence. To investigate its potential effect on hemostasis, we genotyped 865 patients with coronary artery disease (CAD), 915 with myocardial infarction (MI), and 417 control patients (Ludwigshafen Risk and Cardiovascular Health Study) and performed functional studies of this variant. A univariate analysis of male and female carriers of the Tyr2561 allele aged 55 years or younger revealed an elevated risk for repeated MI (odds ratio, 2.53; 95% confidence interval [CI], 1.07-5.98). The odds ratio was even higher in females aged 55 years or younger, at a value of 5.93 (95% CI, 1.12-31.24). Cone and plate aggregometry showed that compared with Phe2561, Tyr2561 was associated with increased platelet aggregate size both in probands' blood and with the recombinant variants. Microfluidic assays revealed that the critical shear rate for inducing aggregate formation was decreased to 50% by Tyr2561 compared with Phe2561. Differences in C-domain circular dichroism spectra resulting from Tyr2561 suggest an increased shear sensitivity of VWF as a result of altered association of the C domains that disrupts the normal dimer interface. In summary, our data emphasize the functional effect of the VWF C4 domain for VWF-mediated platelet aggregation in a shear-dependent manner and provide the first evidence that a functional variant of VWF plays a role in arterial thromboembolism.
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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.