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A single nucleotide polymorphism at nucleotide −1793 in the von Willebrand factor (VWF) regulatory region is associated with plasma VWF:Ag levels
Author(s) -
Harvey Philip J.,
Keightley Angela M.,
Lam Y. Miu,
Cameron Cherie,
Lillicrap David
Publication year - 2000
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2000.02000.x
Subject(s) - single nucleotide polymorphism , von willebrand factor , linkage disequilibrium , snp , biology , platelet , microbiology and biotechnology , glycoprotein , nucleotide , genetics , genotype , immunology , gene
von Willebrand Factor (VWF) is a large multimeric glycoprotein involved in the transport and protection of factor VIII and in mediating platelet–subendothelium and platelet–platelet interactions. We have documented the presence of a single nucleotide polymorphism (SNP) at nucleotide (nt) −1793 (G 0·36 or C 0·64) in the VWF 5′‐flanking sequence. This polymorphism is in strong linkage disequilibrium with the previously reported SNPs at nts −1234, −1185 and −1051 and, like this other group of polymorphisms, shows a significant association with plasma VWF levels. This association is more marked in subjects who are more than 40 years of age. Further, circumstantial evidence to support a role for the −1793 sequence in regulating VWF expression comes from our demonstration of differential binding of endothelial cell nuclear proteins, including the transcription factor NFκB, by this sequence. In summary, the association of the −1793 SNP with plasma VWF levels provides additional evidence for the role of the VWF regulatory region between nts −1793 and −1051 in controlling VWF expression.