Linked Life Data

19875892

Source:http://linkedlifedata.com/resource/pubmed/id/19875892

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2009-10-30
pubmed:abstractText
A daily dose of vitamin K antagonists (VKAs) may vary and its range depends on various interrelated factors. Low responsiveness to VKA (defined as a failure to achieve a target international normalized ratio [INR]) is associated with polymorphisms of the vitamin K epoxide reductase-oxidase complex gene (VKORC1). A highly prevalent promoter single-nucleotide polymorphism (VKORC1-1639 G>A, rs17878363) impairs VKORC1 expression and determines the interindividual variability of the target INR. We studied 57 patients receiving oral anticoagulation, including 50 subjects treated with acenocoumarol (mean dose: 5.7+/-2.3 mg/day) and 7 treated with warfarin (mean dose: 9.6+/-4.2 mg/day). The indications for the use of oral anticoagulant therapy were as follows: deep-vein thrombosis (N = 23); pulmonary embolism (N = 20); arterial thrombosis (N = 5); stroke (N = 4); atrial fibrillation with transient ischemic attacks (N = 2), and history of multiple thromboembolic events (N = 3). Identification of the VKORC1 genomic variation was performed using DNA sequencing methods. The prevalence of the mutated allele (VKORC1 -1639A) was 41%. The VKORC1 -1639G allele carriers required a higher daily dose of acenocoumarol (5.9+/-1.9 mg) than the noncarriers (4.1+/-3.3 mg; P < 0.001). All of 5 low responders (who failed to achieve a target INR using standard dose requirements of VKAs) were homozygous for the 1639G allele. Low responders did not differ from good responders with respect to age, gender, and body mass index. Our findings suggest the potential benefits from pharmacogenetic testing, and provide evidence that the VKORC1 -1639 G>A gene polymorphism may explain at least in part the low responsiveness to acenocoumarol.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1234-1983
pubmed:author
pubmed:issnType
Print
pubmed:volume
50
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
399-403
pubmed:meshHeading
pubmed-meshheading:19875892-Acenocoumarol, pubmed-meshheading:19875892-Adult, pubmed-meshheading:19875892-Alleles, pubmed-meshheading:19875892-Anticoagulants, pubmed-meshheading:19875892-Atrial Fibrillation, pubmed-meshheading:19875892-Base Sequence, pubmed-meshheading:19875892-DNA Primers, pubmed-meshheading:19875892-Dose-Response Relationship, Drug, pubmed-meshheading:19875892-Drug Resistance, pubmed-meshheading:19875892-Female, pubmed-meshheading:19875892-Gene Frequency, pubmed-meshheading:19875892-Humans, pubmed-meshheading:19875892-International Normalized Ratio, pubmed-meshheading:19875892-Male, pubmed-meshheading:19875892-Middle Aged, pubmed-meshheading:19875892-Mixed Function Oxygenases, pubmed-meshheading:19875892-Poland, pubmed-meshheading:19875892-Polymorphism, Single Nucleotide, pubmed-meshheading:19875892-Promoter Regions, Genetic, pubmed-meshheading:19875892-Pulmonary Embolism, pubmed-meshheading:19875892-Venous Thrombosis, pubmed-meshheading:19875892-Vitamin K, pubmed-meshheading:19875892-Warfarin
pubmed:year
2009
pubmed:articleTitle
A vitamin K epoxide reductase-oxidase complex gene polymorphism (-1639G>A) and interindividual variability in the dose-effect of vitamin K antagonists.
pubmed:affiliation
John Paul II Hospital, Krakow, Poland. estepien@szpitaljp2.krakow.pl
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't