Submitted July 12, 2006
Accepted November 12, 2006
The effect of von Willebrand factor Y/C1584 on in
vivo protein level and function, and interaction with ABO blood group
James Anthony Davies, Peter William Collins, Lee Sarah Hathaway, and Derrick John Bowen*
Cardiff University School of Medicine, United Kingdom
University Hospital of Wales, Health Park, United Kingdom
* Corresponding author; email: bowendj1{at}cardiff.ac.uk.
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 are individually causative of disease. We investigated the effect of C1584 alone, and in combination with ABO blood group, on the level and properties of plasma VWF. A cohort of 5052 blood donors was recruited: 50 individuals were heterozygous Y/C1584 and 5002 were homozygous Y/Y1584. The mean VWF:Ag for heterozygotes (82±35 IUdL-1) was significantly lower than for homozygotes (111±37 IUdL-1) (P < 0.0001). For each 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 individuals with VWF:Ag 
50 IUdL-1, 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%), however Y/C1584 in conjunction with group O was strikingly enriched (34.8%). VWF:CB and VWF:RCo were significantly lower for Y/C1584 heterozygotes compared with 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 level in some individuals.
