title: Effect of von Willebrand factor Y/C1584 on in vivo protein level and function and interaction with ABO blood group.
abstract: Blood group O and the cysteine allele of the Y/C1584 change in von Willebrand factor (VWF) are enriched in type 1 VWD, but neither causes disease. We investigated the effect of C1584, alone and in combination with the ABO blood group, on the level and properties of plasma VWF. A cohort of 5052 blood donors was recruited: 50 donors were heterozygous for Y/C1584 and 5002 were homozygous for Y/Y1584. Mean VWF antigen (VWF:Ag) for heterozygotes (82 +/- 35 IUdL(-1)) was significantly lower than for homozygotes (111 +/- 37 IUdL(-1)) (P < .001). Foreach ABO blood group, VWF:Ag was decreased among Y/C1584 heterozygotes compared with Y/Y1584 homozygotes; a larger decrease was observed for group O. Among donors with VWF:Ag levels of 50 IUdL(-1) or lower, Y/C1584 heterozygosity was markedly enriched (18%) compared with the entire cohort (1.5%). Blood group O was enriched to a lesser extent (2.4%), but Y/C1584 in conjunction with group O was strikingly enriched (34.8%). VWF collagen binding activity (VWF:CB) and ristocetin cofactor activity (VWF:RCo) were significantly lower for Y/C1584 heterozygotes than for Y/Y1584 homozygotes, and a qualitative difference in Y/C1584 plasma VWF multimer profile was observed compared with that for Y/Y1584 VWF. The data support a multifactorial basis for low VWF levels in some individuals.
authors.affiliation: Department of Haematology, School of Medicine, Cardiff University, Cardiff, United Kingdom.
authors.forename: James Anthony
authors.initials: JA
authors.lastname: Davies
authors.forename: Peter William
authors.initials: PW
authors.lastname: Collins
authors.forename: Lee Sarah
authors.initials: LS
authors.lastname: Hathaway
authors.forename: Derrick John
authors.initials: DJ
authors.lastname: Bowen
mesh_terms: D000017:ABO Blood-Group System / Q000378:metabolism*; D000483:Alleles; D019943:Amino Acid Substitution; D000941:Antigens / Q000097:blood; D001483:Base Sequence; D015331:Cohort Studies; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D046912:Multiprotein Complexes / Q000097:blood / Q000737:chemistry; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D014852:Wales; D014841:von Willebrand Factor / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000017:ABO Blood-Group System; D000941:Antigens; D017931:DNA Primers; D046912:Multiprotein Complexes; C029417:Von Willebrand antigen; D014841:von Willebrand Factor