Effect of von Willebrand factor Y/C1584 on in vivo protein level and function and interaction with ABO blood group.
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.
Davies
James Anthony
JA
Department of Haematology, School of Medicine, Cardiff University, Cardiff, United Kingdom.
Collins
Peter William
PW
Hathaway
Lee Sarah
LS
Bowen
Derrick John
DJ
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*
D000017:ABO Blood-Group System; D000941:Antigens; D017931:DNA Primers; D046912:Multiprotein Complexes; C029417:Von Willebrand antigen; D014841:von Willebrand Factor