scholarly journals Genetic determinants of von Willebrand factor levels and activity in relation to the risk of cardiovascular disease: a review

2011 ◽  
Vol 9 (5) ◽  
pp. 899-908 ◽  
Author(s):  
M. C. VAN SCHIE ◽  
J. E. VAN LOON ◽  
M. P. M. DE MAAT ◽  
F. W. G. LEEBEEK
Keyword(s):  
Cardiovascular Disease ◽  
Von Willebrand Factor ◽  
Genetic Determinants ◽  
Von Willebrand ◽  
Willebrand Factor

scholarly journals Genetic determinants of VWF clearance and FVIII binding modify FVIII pharmacokinetics in pediatric hemophilia A patients

Blood ◽  
2019 ◽  
Vol 134 (11) ◽  
pp. 880-891 ◽  
Author(s):  
Laura L. Swystun ◽  
Kenichi Ogiwara ◽  
Orla Rawley ◽  
Christine Brown ◽  
Ilinca Georgescu ◽  
...  
Keyword(s):  
Blood Group ◽  
Von Willebrand Factor ◽  
Half Life ◽  
Hemophilia A ◽  
Blood Type ◽  
Abo Blood Group ◽  
Genetic Determinants ◽  
Group Status ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Factor VIII (FVIII) pharmacokinetic (PK) properties show high interpatient variability in hemophilia A patients. Although previous studies have determined that age, body mass index, von Willebrand factor antigen (VWF:Ag) levels, and ABO blood group status can influence FVIII PK, they do not account for all observed variability. In this study, we aim to describe the genetic determinants that modify the FVIII PK profile in a population of 43 pediatric hemophilia A patients. We observed that VWF:Ag and VWF propeptide (VWFpp)/VWF:Ag, but not VWFpp, were associated with FVIII half-life. VWFpp/VWF:Ag negatively correlated with FVIII half-life in patients with non-O blood type, but no correlation was observed for type O patients, suggesting that von Willebrand factor (VWF) half-life, as modified by the ABO blood group, is a strong regulator of FVIII PK. The FVIII-binding activity of VWF positively correlated with FVIII half-life, and the rare or low-frequency nonsynonymous VWF variants p.(Arg826Lys) and p.(Arg852Glu) were identified in patients with reduced VWF:FVIIIB but not VWF:Ag. Common variants at the VWF, CLEC4M, and STAB2 loci, which have been previously associated with plasma levels of VWF and FVIII, were associated with the FVIII PK profile. Together, these studies characterize the mechanistic basis by which VWF clearance and ABO glycosylation modify FVIII PK in a pediatric population. Moreover, this study is the first to identify non-VWF and non-ABO variants that modify FVIII PK in pediatric hemophilia A patients.

Synergic effect of GPIBA and von Willebrand factor in pathogenesis of deep vein thrombosis

Vascular ◽  
2020 ◽  
Vol 28 (3) ◽  
pp. 309-313
Author(s):  
Da Li ◽  
Xiaosong Zhang ◽  
Honggang Zhang ◽  
Xiaoqiang Li
Keyword(s):  
Cardiovascular Disease ◽  
Deep Vein Thrombosis ◽  
Membrane Protein ◽  
Von Willebrand Factor ◽  
Integrin Subunit ◽  
Dynamic Changes ◽  
Vein Thrombosis ◽  
Von Willebrand ◽  
Deep Vein ◽  
Willebrand Factor

Objectives In cardiovascular disease, deep vein thrombosis is one of the vital symptoms causing pulmonary thromboembolism. However, the pathogenesis of deep vein thrombosis is still not clear. One of the critical factors leading to deep vein thrombosis is the platelet aggregation that is mediated by a set of key genes including platelet membrane protein coded by platelet glycoprotein Ib alpha chain (GPIBA). Methods Deep vein thrombosis model was established according to the previous protocol, and venous blood and thrombi were collected for further analysis. Results The dynamic changes of GPIBA and coagulation factor, von Willebrand factor, were observed in deep vein thrombosis models. Meanwhile, critical proteins participating in adhesion and binding of platelets such as epithelial membrane protein 2 (EMP2), vascular cell adhesion protein 1 (VCAM1), immunoreceptor tyrosine-based activation motif 1 (ITAM1), integrin subunit alpha M (ITGAM), or fibronectin were also differentially expressed in deep vein thrombosis models. Conclusions Application of heparin could reverse these dynamic changes in deep vein thrombosis models. Thus, we explained the potential synergic role of GPIBA and von Willebrand factor in regulating the occurrence of deep vein thrombosis and provide therapeutic target against cardiovascular disease.

scholarly journals Von Willebrand Factor, Type 2 Diabetes Mellitus, and Risk of Cardiovascular Disease

Circulation ◽  
2008 ◽  
Vol 118 (24) ◽  
pp. 2533-2539 ◽  
Author(s):  
David S. Frankel ◽  
James B. Meigs ◽  
Joseph M. Massaro ◽  
Peter W.F. Wilson ◽  
Christopher J. O'Donnell ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Type 2 Diabetes Mellitus ◽  
Von Willebrand Factor ◽  
Factor Type ◽  
Von Willebrand ◽  
Willebrand Factor

scholarly journals Genetic determinants of plasma von Willebrand factor antigen levels: a target gene SNP and haplotype analysis of ARIC cohort

Blood ◽  
2011 ◽  
Vol 117 (19) ◽  
pp. 5224-5230 ◽  
Author(s):  
Marco Campos ◽  
Wei Sun ◽  
Fuli Yu ◽  
Maja Barbalic ◽  
Weihong Tang ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Von Willebrand Disease ◽  
Blood Type ◽  
Nucleotide Polymorphisms ◽  
Genetic Determinants ◽  
Single Nucleotide ◽  
Distinct Haplotype ◽  
Von Willebrand ◽  
And Storage ◽  
Willebrand Factor

Abstractvon Willebrand factor (VWF) is an essential component of hemostasis and has been implicated in thrombosis. Multimer size and the amount of circulating VWF are known to impact hemostatic function. We associated 78 VWF single nucleotide polymorphisms (SNPs) and haplotypes constructed from those SNPs with VWF antigen level in 7856 subjects of European descent. Among the nongenomic factors, age and body mass index contributed 4.8% and 1.6% of VWF variation, respectively. The SNP rs514659 (tags O blood type) contributed 15.4% of the variance. Among the VWF SNPs, we identified 18 SNPs that are associated with levels of VWF. The correlative SNPs are either intronic (89%) or silent exonic (11%). Although SNPs examined are distributed throughout the entire VWF gene without apparent cluster, all the positive SNPs are located in a 50-kb region. Exons in this region encode for VWF D2, D′, and D3 domains that are known to regulate VWF multimerization and storage. Mutations in the D3 domain are also associated with von Willebrand disease. Fifteen of these 18 correlative SNPs are in 2 distinct haplotype blocks. In summary, we identified a cluster of intronic VWF SNPs that associate with plasma levels of VWF, individually or additively, in a large cohort of healthy subjects.

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