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Updated: Jan 10, 2026

Investigating von Willebrand Factor Pathophysiology Using a Flow Chamber Model of von Willebrand Factor-platelet String Formation
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Investigating von Willebrand Factor Pathophysiology Using a Flow Chamber Model of von Willebrand Factor-platelet String Formation

Published on: August 14, 2017

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A non-coding ABO regulatory variant associated with VWF levels, thrombosis risk, and COVID-19 severity is

Douglas Victorino Esposito1, Hellen Ferreira de Souza Sobrinho1, Marcelo Rocha Marques2

  • 1Oral Biology Program, Piracicaba Dental School, University of Campinas, Piracicaba, São Paulo, Brazil.

HGG Advances
|November 28, 2025
PubMed

Venous thromboembolism (VTE) is a major cause of mortality, influenced by genetic and environmental factors. von Willebrand factor (VWF) mediates hemostasis by promoting platelet adhesion, and its plasma levels are associated with thrombotic risk. Although many non-coding variants in ABO are associated with VWF levels, VTE risk, and COVID-19 severity, the mechanisms underlying these associations remain unclear. In this study, we identified the ABO locus as the genomic region with the highest concentration of variants associated with VWF levels. Chromatin conformation analyses in endothelial cells revealed non-coding ABO variants (rs657152, rs9411377, rs660340, and rs505922) associated with VWF levels, VTE risk, and COVID-19 severity, located in spatial proximity to ADAMTS13. ADAMTS13 is a key regulator of VWF activity, and both ADAMTS13 and VWF play crucial roles in coagulation and thrombosis. Chromatin activation (CRISPRa) of the region near the non-coding ABO variant rs657152 increased ADAMTS13 transcription in endothelial cells, suggesting that this variant resides in a regulatory region with the potential to modulate long-range transcriptional control of ADAMTS13. Luciferase assay revealed reduced transcriptional activity driven by the rs505922-C allele in endothelial cells. These findings provide insights into the spatial organization of the ABO locus and its potential role in ADAMTS13 regulation.

Keywords:
ABOADAMTS13COVID-19CRISPRacis-regulatory elementendothelial cellsgenetic variantsluciferasethrombosisvon Willebrand Factor

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