The Impacts of Genetic Polymorphisms on the Von Willebrand Factor Level in Type 1 Von Willebrand Disease

Background: In type 1 von Willebrand disease (VWD), there are only 53-81% patient with found mutations of VWF gene. There were 7 genetic variants of single nucleotide polymorphism (SNP) re-ported to be associated with the variation of VWF levels, including CLEC4M, STXBP5, SCARA5, ABO, VWF, STAB2 and UFM1.Aims: This study were to explore the frequency and impacts of the 7 genes SNPs on VWF level in type 1 VWD patients.Methods: There were 62 patients (M/F: 1) with type 1 VWD en-rolled in this study, including 32 (51.6%) patients with found muta-tions of VWF gene. The patients’ VWF levels of both VWF:Ag and VWF activity (VWF:ACL or VWF:RCo) and FVIII: C were retrospec-tively collected and analyzed. Each enrolled patient's SNPs of the 7 genes were targeted by PCR followed by direct sequencing.Results: The patients without variant (A/A) of UFM1 has signifi-cantly lower median VWF:Ag than variant (A/C) type (33% vs 44.7%, p = 0.038, Figure 1A). Patients without variant (A/A) of STXBP gene had both significantly lower median value of VWF:Ag (31.9% vs 46.1%, p = 0.019, Figure 1B) and VWF activity (26.55% vs 30.4%, p = 0.0419, Figure 1C) than variant (A/G). Four alleles substitution of SNP of UFM1(C>A) and STXBP genes (G>A) variant has remarkably and significantly lowest median VWF antigen level as compared to three and two substitutions (Figure 2)