1. The common VWF single nucleotide variants c. 2365A>G and c
The common VWF single nucleotide variants c.2365A>G and c.2385T>C modify VWF biosynthesis and clearance
by Ahmad H. Mufti, Kenichi Ogiwara, Laura L. Swystun, Jeroen C. J. Eikenboom, Ulrich Budde, Wilma M. Hopman, Christer Halldén, Jenny Goudemand, Ian R. Peake, Anne C. Goodeve, David Lillicrap, and Daniel J. Hampshire
BloodAdv
Volume 2(13):
July 10, 2018
© 2018 by The American Society of Hematology

2. Ahmad H. Mufti et al. Blood Adv 2018;2:1585-1594
© 2018 by The American Society of Hematology

3. Association between SNV genotype and median VWF:Ag and FVIII:C levels in HCs. (A) SNV c.2365A>G and VWF:Ag levels.
Association between SNV genotype and median VWF:Ag and FVIII:C levels in HCs. (A) SNV c.2365A>G and VWF:Ag levels. (B) SNV c.2385T>C and VWF:Ag levels. (C) Both SNVs in cis and VWF:Ag levels. (D) SNV c.2365A>G and FVIII:C levels. (E) SNV c.2385T>C and FVIII:C levels. (F) Both SNVs in cis and FVIII:C levels. Genotypes compared using a Mann-Whitney U test (*P < .05; ****P < .0001). Bars indicate 95% CI. NR, nonreference allele; ns, not significant; R, reference allele.
Ahmad H. Mufti et al. Blood Adv 2018;2:
© 2018 by The American Society of Hematology

4. In vitro expression of recombinant VWF protein.
In vitro expression of recombinant VWF protein. (A) SNV c.2365A>G. (B) SNV c.2385T>C. (C) Both SNVs in cis. Genotypes compared using a 2-way ANOVA with the Tukey multiple comparisons test (*P < .05; **P < .01; ***P < .001; ****P < .0001). Mean values for n = 3 triplicate measurements are shown (bars indicate standard error of the mean).
Ahmad H. Mufti et al. Blood Adv 2018;2:
© 2018 by The American Society of Hematology

5. In vitro expression of recombinant VWF mRNA.
In vitro expression of recombinant VWF mRNA. (A) SNV c.2365A>G. (B) SNV c.2385T>C. (C) Both SNVs in cis. Genotypes compared using an unpaired Student t test (*P < .05; **P < .01; ****P < .0001). Mean values for n = 3 triplicate measurements are shown (bars indicate standard error of the mean).
Ahmad H. Mufti et al. Blood Adv 2018;2:
© 2018 by The American Society of Hematology

6. mRNA half-life of recombinant VWF
mRNA half-life of recombinant VWF. WT VWF (half-life [t1/2] = 2:36 hours) compared against (A) SNV c.2365A>G (t1/2 = 2:51 hours; 8.1% increase); (B) SNV c.2385T>C (t1/2 = 2:49 hours; 7.7% increase).
mRNA half-life of recombinant VWF. WT VWF (half-life [t1/2] = 2:36 hours) compared against (A) SNV c.2365A>G (t1/2 = 2:51 hours; 8.1% increase); (B) SNV c.2385T>C (t1/2 = 2:49 hours; 7.7% increase). (C) Both SNVs in cis (t1/2 = 2:54 hours; 10.0% increase). (D) Comparison of fold change in mRNA half-life between genotypes. Genotypes compared using an unpaired Student t test (*P < .05; **P < .01). Bars indicate standard error of the mean.
Ahmad H. Mufti et al. Blood Adv 2018;2:
© 2018 by The American Society of Hematology

7. Association between SNV c
Association between SNV c.[2365A>G;2385T>C] genotype and median VWFpp/VWF:Ag ratio in healthy controls.
Association between SNV c.[2365A>G;2385T>C] genotype and median VWFpp/VWF:Ag ratio in healthy controls. Genotypes compared using a Mann-Whitney U test (**P < .01). Bars indicate 95% CI.
Ahmad H. Mufti et al. Blood Adv 2018;2:
© 2018 by The American Society of Hematology

8. Influence of SNV on VWF expression and half-life in a murine model.
Influence of SNV on VWF expression and half-life in a murine model. (A) Alignment of VWF amino acids p across species. (B) Alignment of VWF nucleotides c between human and mouse. (C) Expression of murine c.[2365G>A;2367T>C], c.2385C>T and c.[2365G>A;2367T>C;2385C>T] in vivo. **P < (D) Expression of wild-type and c.[2365G>A;2367T>C;2385C>T] murine VWF 4 weeks posthydrodynamic injection. (E) Half-life of plasma-derived murine VWF in VWF knockout mice. (F) Stabilization of endogenous FVIII:C in VWF knockout mice.
Ahmad H. Mufti et al. Blood Adv 2018;2:
© 2018 by The American Society of Hematology