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Status: Bibliographieeintrag

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Verfasst von:Schneppenheim, Reinhard [VerfasserIn]   i
 Huck, Volker [VerfasserIn]   i
 März, Winfried [VerfasserIn]   i
Titel:The von Willebrand factor Tyr2561 allele is a gain-of-function variant and a risk factor for early myocardial infarction
Verf.angabe:Reinhard Schneppenheim, Natalie Hellermann, Maria A. Brehm, Ulrike Klemm, Tobias Obser, Volker Huck, Stefan W. Schneider, Cécile V. Denis, Alexander Tischer, Matthew Auton, Winfried März, Emma-Ruoqi Xu, Matthias Wilmanns, and Rainer B. Zotz
Jahr:2019
Umfang:11 S.
Fussnoten:Online October 26, 2018 ; Gesehen am 28.02.2019
Titel Quelle:Enthalten in: Blood
Ort Quelle:Washington, DC : American Society of Hematology, 1946
Jahr Quelle:2019
Band/Heft Quelle:133(2019), 4, Seite 356-365
ISSN Quelle:1528-0020
Abstract:Visual Abstract. <img class="highwire-fragment fragment-image" alt="Figure1" src="http://www.bloodjournal.org/content/bloodjournal/133/4/356/F1.medium.gif" width="440" height="264"/>Download figureOpen in new tabDownload powerpoint. 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.
DOI:doi:10.1182/blood-2018-04-843425
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: http://dx.doi.org/10.1182/blood-2018-04-843425
 Volltext: http://www.bloodjournal.org/content/133/4/356
 DOI: https://doi.org/10.1182/blood-2018-04-843425
Datenträger:Online-Ressource
Sprache:eng
K10plus-PPN:1588218880
Verknüpfungen:→ Zeitschrift

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