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WFRF:(Hampshire Daniel J)
 

Sökning: WFRF:(Hampshire Daniel J) > (2018) > The common VWF sing...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00003673naa a2200433 4500
001oai:researchportal.hkr.se/admin:publications/1c2ebdcb-591e-49c1-9883-7fa5fbf7e880
003SwePub
008240515s2018 | |||||||||||000 ||eng|
0247 a oai:researchportal.hkr.se/admin:publications/1c2ebdcb-591e-49c1-9883-7fa5fbf7e8802 URI
0247 a https://doi.org/10.1182/bloodadvances.20170116432 DOI
040 a (SwePub)hkr
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Mufti, Ahmad Hu England4 aut
2451 0a The common VWF single nucleotide variants c.2365A>G and c.2385T>C modify VWF biosynthesis and clearance
264 c 2018-07-06
264 1b Elsevier BV,c 2018
300 a 9
520 a Plasma levels of von Willebrand factor (VWF) vary considerably in the general population and this variation has been linked to several genetic and environmental factors. Genetic factors include 2 common single nucleotide variants (SNVs) located in VWF, rs1063856 (c.2365A>G) and rs1063857 (c.2385T>C), although to date the mechanistic basis for their association with VWF level is unknown. Using genotypic/phenotypic information from a European healthy control population, in vitro analyses of recombinant VWF expressing both SNVs, and in vivo murine models, this study determined the precise nature of their association with VWF level and investigated the mechanism(s) involved. Possession of either SNV corresponded with a significant increase in plasma VWF in healthy controls (P < .0001). In vitro expression confirmed this observation and highlighted an independent effect for each SNV (P < .0001 and P < .01, respectively), despite close proximity and strong linkage disequilibrium between them both. The influence of c.2365A>G on VWF levels was also confirmed in vivo. This increase in VWF protein corresponded to an increase in VWF messenger RNA (mRNA) resulting, in part, from prolonged mRNA half-life. In addition, coinheritance of both SNVs was associated with a lower VWF propeptide-to-VWF antigen ratio in healthy controls (P < .05) and a longer VWF half-life in VWF knockout mice (P < .0001). Both SNVs therefore directly increase VWF plasma levels through a combined influence on VWF biosynthesis and clearance, and may have an impact on disease phenotype in both hemostatic and thrombotic disorders.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Medicinsk bioteknologix Biomedicinsk laboratorievetenskap/teknologi0 (SwePub)304022 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Medical Biotechnologyx Biomedical Laboratory Science/Technology0 (SwePub)304022 hsv//eng
7001 a Ogiwara, Kenichiu Canada,Kanada4 aut
7001 a Swystun, Laura Lu Canada,Kanada4 aut
7001 a Eikenboom, Jeroen C Ju Netherlands,Nederländerna4 aut
7001 a Budde, Ulrichu Germany,Tyskland4 aut
7001 a Hopman, Wilma Mu Canada,Kanada4 aut
7001 a Halldén, Cu Biomedicin4 aut0 (Swepub:hkr)9f106859-211e-4907-96a5-55f48cf6d357
7001 a Goudemand, Jennyu France,Frankrike4 aut
7001 a Peake, Ian Ru England4 aut
7001 a Goodeve, Anne Cu England4 aut
7001 a Lillicrap, Davidu Canada,Kanada4 aut
7001 a Hampshire, Daniel Ju England4 aut
7102 a Englandb Canada4 org
7730 t Blood Advancesd : Elsevier BVg 2:13, s. 1585-1594q 2:13<1585-1594x 2473-9529x 2473-9537
8564 u https://europepmc.org/articles/pmc6039659?pdf=render
8564 8u oai:researchportal.hkr.se/admin:publications/1c2ebdcb-591e-49c1-9883-7fa5fbf7e880
8564 8u https://doi.org/10.1182/bloodadvances.2017011643

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