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An association between the L1565 variant of von Willebrand factor and susceptibility to proteolysis by ADAMTS13

From the Department of Hematology, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK

Correspondence: Derrick J. Bowen, Department of Haematology, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK, E-mail: bowendj1{at}cf.ac.uk

The cysteine allele of the amino acid polymorphism (AAP) Y/C1584 in the A2 domain of von Willebrand factor (VWF) has been shown to correlate with enhanced VWF proteolysis by ADAMTS13. The frequencies and effect on VWF proteolysis of six reported AAP in VWF domains A1 and A2 were investigated. Only two AAP were variant: 4414 G/C (D/H1472) (allele frequency 0.86/0.14) and 4693 G/T (V/L1565) (allele frequency 0.92/0.08). D/H1472 had no apparent effect on VWF proteolysis. For V/L1565, a small but statistically significant increase in proteolysis was observed for V/L1565 VWF compared with V/V1565 VWF (p=0.0004).

Key words: von Willebrand factor, ADAMTS13, proteolysis, Y/C1584, V/L1565.