Source:http://linkedlifedata.com/resource/pubmed/id/11943934
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
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| pubmed:dateCreated |
2002-4-10
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| pubmed:abstractText |
Recently, new missense mutations in the activated protein C (APC) cleavage sites of human factor V (FV) distinct from the R506Q (FV Leiden) mutation have been reported. These mutations affect the APC cleavage site at arginine (Arg) 306 in the heavy chain of activated FV. Whether these mutations result in APC resistance and are associated with a risk of thrombosis is not clear. The main objective of the present study was to identify the APC-resistant phenotype of FV molecules with different mutations in APC cleavage sites. To study this, recombinant FV mutants were reconstituted in FV-deficient plasma, after which normalized APC-sensitivity ratios (n-APC-SRs) were measured in activated partial thromboplastin time-based and Russell's Viper Venom time-based APC-resistance tests. The mutations introduced in FV were R306G, R306T, R506Q, R679A and combinations of these mutations. Based on the APC-sensitivity ratios, we conclude that the naturally occurring mutations at Arg306 (i.e. FV HongKong and FV Cambridge) result in a mildly reduced sensitivity for APC (n-APC-SR, 0.74-0.87), whereas much lower values (n-APC-SR, 0.41-0.51) are obtained for the mutation at Arg506 (FV Leiden). No effect on the n-APC-SR was observed for the recombinant FV mutant containing the single Ala679 mutation. Because reduced sensitivity for APC, not due to FV Leiden, is a risk factor for venous thrombosis, these data suggest that mutations at Arg306 might be associated with a mild risk of venous thrombosis.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Codon,
http://linkedlifedata.com/resource/pubmed/chemical/Factor V,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/factor V Leiden
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| pubmed:status |
MEDLINE
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| pubmed:month |
Apr
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| pubmed:issn |
0957-5235
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
13
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
207-15
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:11943934-Activated Protein C Resistance,
pubmed-meshheading:11943934-Amino Acid Substitution,
pubmed-meshheading:11943934-Animals,
pubmed-meshheading:11943934-COS Cells,
pubmed-meshheading:11943934-Cercopithecus aethiops,
pubmed-meshheading:11943934-Codon,
pubmed-meshheading:11943934-Factor V,
pubmed-meshheading:11943934-Glycosylation,
pubmed-meshheading:11943934-Humans,
pubmed-meshheading:11943934-Mutagenesis, Site-Directed,
pubmed-meshheading:11943934-Mutation, Missense,
pubmed-meshheading:11943934-Partial Thromboplastin Time,
pubmed-meshheading:11943934-Point Mutation,
pubmed-meshheading:11943934-Protein Isoforms,
pubmed-meshheading:11943934-Protein Processing, Post-Translational,
pubmed-meshheading:11943934-Prothrombin Time,
pubmed-meshheading:11943934-Recombinant Fusion Proteins,
pubmed-meshheading:11943934-Structure-Activity Relationship,
pubmed-meshheading:11943934-Transfection
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| pubmed:year |
2002
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| pubmed:articleTitle |
The activated protein C (APC)-resistant phenotype of APC cleavage site mutants of recombinant factor V in a reconstituted plasma model.
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| pubmed:affiliation |
Hemostasis and Thrombosis Research Center, Department of Hematology, LUMC, Leiden, The Netherlands. mneut@lumc.nl
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| pubmed:publicationType |
Journal Article,
Comparative Study
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