CLEC4M and STXBP5 gene variations contribute to von Willebrand factor level variation in von Willebrand disease. (9th May 2015)

• Record Type: Journal Article
• Authors: Sanders, Y. V.; van der Bom, J. G.; Isaacs, A.; Cnossen, M. H.; de Maat, M. P. M.; Laros‐van Gorkom, B. A. P.; Fijnvandraat, K.; Meijer, K.; van Duijn, C. M.; Mauser‐Bunschoten, E. P.; Eikenboom, J.; Leebeek, F. W. G.; the WiN Study Group; Coppens, M.; Kors, A.; de Meris, J.; Nijziel, M. R.; Tamminga, R. Y. J.; Ypma, P. F.; Smiers, F. J. W.; Granzen, B.; Hamulyák, K.; Brons, P.
• Is Part Of: Journal of thrombosis and haemostasis. Volume 13:Number 6(2015:Jun.)
• Page Start: 956
• Page End: 966
• Publication Date: 2015-05-09
• Subjects: Thrombosis -- Periodicals; Hemostasis -- Periodicals; Blood coagulation disorders -- Periodicals; 616.1
• DOI: 10.1111/jth.12927
• Languages: English
• ISSNs: 1538-7933

Abstract

<abstract abstract-type="main" id="jth12927-abs-0001"> <title>Summary</title> <sec id="jth12927-sec-0001" sec-type="section"> <title>Background</title> <p>von Willebrand factor (VWF) levels in healthy individuals are influenced by variations in genetic loci other than the <italic>VWF</italic> gene, whose contribution to VWF levels in patients with von Willebrand disease (VWD) is largely unknown.</p> </sec> <sec id="jth12927-sec-0002" sec-type="section"> <title>Objectives</title> <p>To investigate the association between single‐nucleotide polymorphisms (SNPs), VWF levels, and bleeding phenotype.</p> </sec> <sec id="jth12927-sec-0003" sec-type="section"> <title>Patients/Methods</title> <p>In 364 type 1 VWD and 240 type 2 VWD patients from the nationwide cross‐sectional 'Willebrand in The Netherlands' (WiN) study, we studied the association between eight SNPs in <italic>STXBP5</italic>, <italic> SCARA5</italic>, <italic> ABO</italic>, <italic> VWF</italic>, <italic> STAB2</italic>, <italic> STX2</italic>, <italic> TC2N</italic>, and <italic>CLEC4M</italic>, and VWF antigen (VWF:Ag), VWF activity (VWF:Act), and bleeding phenotype as assessed with the Tosetto bleeding score.</p> </sec> <sec id="jth12927-sec-0004" sec-type="section"> <title>Results</title> <p>In type 1 patients, <italic>STXBP5</italic> was associated with a lower VWF:Ag level (adjusted difference of −3.0 IU dL<sup>−1</sup> per allele; 95% confidence interval [CI] −6.0 to 0.1) and <italic>CLEC4M</italic> with both a lower VWF:Ag level (−4.3 IU dL<sup>−1</sup> per allele; 95% CI −7.9 to −0.6) and lower VWF:Act (−5.7 IU dL<sup>−1</sup> per allele; 95% CI −10.9 to −0.5). In type 2 patients, none of the SNPs was associated with VWF levels. None of the genetic variants was associated with bleeding score.</p> </sec> <sec id="jth12927-sec-0005" sec-type="section"> <title>Conclusions</title> <p>Genetic variations in <italic>STXBP5</italic> and <italic>CLEC4M</italic> are associated with VWF level variation in type 1 VWD, but not in type 2 VWD. This study increases our understanding of the pathophysiology of VWD, and provides a further indication of the involvement of <italic>STXBP5</italic> and <italic>CLEC4M</italic> in determining VWF levels in VWD.</p> </sec> </abstract>