A single nucleotide polymorphism at nucleotide-1793 in the von Willebrand factor (VWF) regulatory region is associated with plasma VWF : Ag levels

von Willebrand Factor (VWF) is a large multimeric glycoprotein involved in the transport and protection of factor VIII and in mediating platlet-subend othelium and platelet-platelet interactions, We have documented the presenc e of a single nucleotide polymorphism (SNP) at nucleotide (nt) -1793 (G 0.3 6 or C 0.64) in the VWF 5'-flanking sequence. This polymorphism is in stron g linkage disequilibrium with the previously reported SNPs at nts -1234, -1 185 and -1051 and, like this other group of polymorphisms, shows a signific ant association with plasma VWF levels. This association is more marked in subjects who are more than 40 years of age. Further, circumstantial evidenc e to support a role for the -1793 sequence in regulating VWF expression com es from our demonstration of differential binding of endothelial cell nucle ar proteins, including the transcription factor NF kappa B, by this sequenc e. In summary the association of the -1793 SNP with plasma VWF levels provi des additional evidence for the role of the VWF regulatory region between n ts -1793 and -1051 in controlling VWF expression.