Source:http://linkedlifedata.com/resource/pubmed/id/15883587
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2005-7-25
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pubmed:abstractText |
We report a novel combination of factors that explains almost 60% of variable response to warfarin. Warfarin is a widely used anticoagulant, which acts through interference with vitamin K epoxide reductase that is encoded by VKORC1. In the next step of the vitamin K cycle, gamma-glutamyl carboxylase encoded by GGCX uses reduced vitamin K to activate clotting factors. We genotyped 201 warfarin-treated patients for common polymorphisms in VKORC1 and GGCX. All the five VKORC1 single-nucleotide polymorphisms covary significantly with warfarin dose, and explain 29-30% of variance in dose. Thus, VKORC1 has a larger impact than cytochrome P450 2C9, which explains 12% of variance in dose. In addition, one GGCX SNP showed a small but significant effect on warfarin dose. Incorrect dosage, especially during the initial phase of treatment, carries a high risk of either severe bleeding or failure to prevent thromboembolism. Genotype-based dose predictions may in future enable personalised drug treatment from the start of warfarin therapy.
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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/Anticoagulants,
http://linkedlifedata.com/resource/pubmed/chemical/Carbon-Carbon Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/Mixed Function Oxygenases,
http://linkedlifedata.com/resource/pubmed/chemical/Warfarin,
http://linkedlifedata.com/resource/pubmed/chemical/glutamyl carboxylase,
http://linkedlifedata.com/resource/pubmed/chemical/vitamin K epoxidase
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pubmed:status |
MEDLINE
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pubmed:issn |
1470-269X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
5
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
262-70
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:15883587-Adult,
pubmed-meshheading:15883587-Aged,
pubmed-meshheading:15883587-Aged, 80 and over,
pubmed-meshheading:15883587-Anticoagulants,
pubmed-meshheading:15883587-Carbon-Carbon Ligases,
pubmed-meshheading:15883587-Dose-Response Relationship, Drug,
pubmed-meshheading:15883587-Female,
pubmed-meshheading:15883587-Haplotypes,
pubmed-meshheading:15883587-Humans,
pubmed-meshheading:15883587-Male,
pubmed-meshheading:15883587-Middle Aged,
pubmed-meshheading:15883587-Mixed Function Oxygenases,
pubmed-meshheading:15883587-Polymorphism, Single Nucleotide,
pubmed-meshheading:15883587-Regression Analysis,
pubmed-meshheading:15883587-Warfarin
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pubmed:year |
2005
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pubmed:articleTitle |
Common VKORC1 and GGCX polymorphisms associated with warfarin dose.
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pubmed:affiliation |
Department of Medical Sciences, Clinical Pharmacology, University Hospital, Uppsala, Sweden. mia.wadelius@medsci.uu.se
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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