Common VWF exon 28 polymorphisms in African Americans affecting the VWF activity assay by ristocetin cofactor. Blood 2010 Jul 15;116(2):280-6
Date
03/17/2010Pubmed ID
20231421Pubmed Central ID
PMC2910611DOI
10.1182/blood-2009-10-249102Scopus ID
2-s2.0-77955499972 (requires institutional sign-in at Scopus site) 161 CitationsAbstract
The diagnosis of von Willebrand disease relies on abnormalities in specific tests of von Willebrand factor (VWF), including VWF antigen (VWF:Ag) and VWF ristocetin cofactor activity (VWF:RCo). When examining healthy controls enrolled in the T. S. Zimmerman Program for the Molecular and Clinical Biology of von Willebrand disease, we, like others, found a lower mean VWF:RCo compared with VWF:Ag in African American controls and therefore sought a genetic cause for these differences. For the African American controls, the presence of 3 exon 28 single nucleotide polymorphisms (SNPs), I1380V, N1435S, and D1472H, was associated with a significantly lower VWF:RCo/VWF:Ag ratio, whereas the presence of D1472H alone was associated with a decreased ratio in both African American and Caucasian controls. Multivariate analysis comparing race, SNP status, and VWF:RCo/VWF:Ag ratio confirmed that only the presence of D1472H was significant. No difference was seen in VWF binding to collagen, regardless of SNP status. Similarly, no difference in activity was seen using a GPIb complex-binding assay that is independent of ristocetin. Because the VWF:RCo assay depends on ristocetin binding to VWF, mutations (and polymorphisms) in VWF may affect the measurement of "VWF activity" by this assay and may not reflect a functional defect or true hemorrhagic risk.
Author List
Flood VH, Gill JC, Morateck PA, Christopherson PA, Friedman KD, Haberichter SL, Branchford BR, Hoffmann RG, Abshire TC, Di Paola JA, Hoots WK, Leissinger C, Lusher JM, Ragni MV, Shapiro AD, Montgomery RRAuthors
Brian Branchford MD Associate Professor in the Pediatrics department at Medical College of WisconsinVeronica H. Flood MD Chief, Professor in the Pediatrics department at Medical College of Wisconsin
Kenneth D. Friedman MD Professor in the Medicine department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Crotalid VenomsExons
Humans
Platelet Function Tests
Polymerase Chain Reaction
Polymorphism, Single Nucleotide
Ristocetin
von Willebrand Diseases
von Willebrand Factor
