Source:http://linkedlifedata.com/resource/pubmed/id/11204592
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
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| pubmed:dateCreated |
2001-2-1
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| pubmed:abstractText |
Carriership of the factor V (FV) gene marked by the R2-haplotype, a series of linked polymorphisms encoding several amino acid changes in FV, is associated with mild resistance to activated protein C (APC) and with an increased risk of thrombosis. We compared the functional properties of normal FV(a) and R2-FV(a) in model systems and in plasma. FV and R2-FV were equally well activated by thrombin and expressed identical cofactor activities in prothrombin activation. Rate constants of APC-catalyzed inactivation of FVa and R2-FVa were similar both with and without protein S. However, significant differences were observed between haemostatic parameters determined in plasma from homozygous carriers of the R2-gene (n = 5) and age-matched non-carriers (n = 19). Plasma from R2-carriers contained significantly lower FV levels and the ratio of the two FV isoforms (FV1 and FV2) was shifted in favor of FV1. The FV2/FV1 ratio was 1.4 (95% CI = 1.3-1.5) in homozygous carriers of R2 and 2.8 (95% CI = 2.5-3.1) in controls (p < 0.00001). In an APC resistance test which quantifies the cofactor activity of FV in APC-catalyzed FVIII(a) inactivation, homozygous R2-carriers had significantly lower (p < 0.00001) APC sensitivity ratios (APCsr = 1.54, 95% CI = 1.48-1.60) than controls (APCsr = 2.17, 95% CI = 2.05-2.28). This indicates that R2-FV has reduced cofactor activity in APC-catalyzed FVIII(a) inactivation. The changes of the relative amounts of FV1 and FV2 in carriers of the R2-gene will result in increased thrombin formation in the presence of APC and may provide a mechanistic explanation for the increased thrombotic risk associated with the R2-haplotype.
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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/Factor V,
http://linkedlifedata.com/resource/pubmed/chemical/Factor Va,
http://linkedlifedata.com/resource/pubmed/chemical/Factor Xa,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/Protein S,
http://linkedlifedata.com/resource/pubmed/chemical/Prothrombin
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jan
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| pubmed:issn |
0340-6245
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
85
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
75-81
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:11204592-Activated Protein C Resistance,
pubmed-meshheading:11204592-Adult,
pubmed-meshheading:11204592-Blood Coagulation Tests,
pubmed-meshheading:11204592-Dose-Response Relationship, Drug,
pubmed-meshheading:11204592-Factor V,
pubmed-meshheading:11204592-Factor Va,
pubmed-meshheading:11204592-Factor Xa,
pubmed-meshheading:11204592-Female,
pubmed-meshheading:11204592-Gene Expression Regulation,
pubmed-meshheading:11204592-Genotype,
pubmed-meshheading:11204592-Haplotypes,
pubmed-meshheading:11204592-Humans,
pubmed-meshheading:11204592-Kinetics,
pubmed-meshheading:11204592-Male,
pubmed-meshheading:11204592-Middle Aged,
pubmed-meshheading:11204592-Protein Isoforms,
pubmed-meshheading:11204592-Protein S,
pubmed-meshheading:11204592-Prothrombin,
pubmed-meshheading:11204592-Thrombosis
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| pubmed:year |
2001
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| pubmed:articleTitle |
Functional properties of factor V and factor Va encoded by the R2-gene.
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| pubmed:affiliation |
Department of Biochemistry, Cardiovascular Research Institute, Maastricht, Maastricht University, The Netherlands.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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