title: Oligosaccharide structures of von Willebrand factor and their potential role in von Willebrand disease.
abstract: Oligosaccharides make up approximately 20% of the mass of VWF and although their structures are well established, their functional role remains unclear. Modification of the VWF oligosaccharide structures has been shown to result in increased plasma clearance of the protein. A mutation which alters cell type-specific expression of the Galgt2 glycosyltransferase gene in the RIIIS/J mouse results in an autosomal dominant partial quantitative deficiency of VWF. Increased plasma clearance of VWF has been demonstrated in some individuals with a partial quantitative deficiency of the protein and it is possible that variation in VWF glycosylation may contribute towards this. ABH antigens occur within the oligosaccharide component of VWF and may account for the variation in plasma VWF:Ag levels observed between individuals of different ABO blood groups. The structures and functional roles of the oligosaccharide side chains of VWF and possible pathogenetic mechanisms by which they may contribute towards VWD are reviewed in this article.
authors.affiliation: The Katharine Dormandy Haemophilia Centre and Haemostasis Unit, Royal Free and University College Medical School, Pond Street, London NW3 2QG, UK. carolyn.millar@royalfree.nhs.uk
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Millar
authors.forename: Simon A
authors.initials: SA
authors.lastname: Brown
mesh_terms: D000017:ABO Blood-Group System / Q000378:metabolism; D000818:Animals; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D016695:Glycosyltransferases / Q000172:deficiency / Q000378:metabolism; D006801:Humans; D007519:Isoantigens / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D025942:Oligosaccharides, Branched-Chain / Q000235:genetics* / Q000378:metabolism; D046188:Protein Modification, Translational / Q000235:genetics*; D014842:von Willebrand Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014841:von Willebrand Factor / Q000235:genetics* / Q000378:metabolism
chemical_list: D000017:ABO Blood-Group System; D007519:Isoantigens; D025942:Oligosaccharides, Branched-Chain; D014841:von Willebrand Factor; D016695:Glycosyltransferases; C505903:Galgt2 protein, mouse