C1584: effect on von Willebrand factor proteolysis and von Willebrand factor antigen levels.
The present review provides a clearer picture of the effect of C1584 on the level and properties of von Willebrand factor (VWF). The C1584 variant is associated with decreased VWF levels (especially in combination with blood group O) and VWF function, and with slightly enhanced VWF proteolysis, and there is evidence to support its association with enhanced VWF clearance. These properties help explain the enrichment for C1584 in mild type 1 VWD and the observed marked association of the variant and blood group O in this mild bleeding disorder. It has been proposed that the mildly enhanced VWF proteolysis associated with C1584 (and also with blood group O) may compromise clot formation, offering a further rationale for the enrichment of the variant in type 1 VWD. C1584 shows variable penetrance and this is still not fully understood. It reflects the interaction of C1584 with other variables, one of which is clearly blood group O. Genome-wide association studies aimed at identifying loci involved in the control of the VWF level may provide further insights into C1584 penetrance and, more generally, into mechanisms underlying type 1 VWD and also cardiovascular disease.
Davies
James Anthony
JA
Department of Haematology, School of Medicine, Cardiff University, Heath Park, Cardiff, UK.
Collins
Peter William
PW
Hathaway
Lee Sarah
LS
Bowen
Derrick John
DJ
D000017:ABO Blood-Group System / Q000235:genetics; D051722:ADAM Proteins / Q000378:metabolism; D000071120:ADAMTS13 Protein; D019943:Amino Acid Substitution; D001777:Blood Coagulation; D015331:Cohort Studies; D005808:Genes, Recessive; D005838:Genotype; D006801:Humans; D008657:Metabolic Clearance Rate; D020125:Mutation, Missense; D019683:Penetrance; D010641:Phenotype; D017354:Point Mutation; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D014842:von Willebrand Diseases / Q000235:genetics*; D014841:von Willebrand Factor / Q000032:analysis / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
D000017:ABO Blood-Group System; D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human