Linked Life Data

20205664

Source:http://linkedlifedata.com/resource/pubmed/id/20205664

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-3-8
pubmed:abstractText
The identification of the genes encoding CYP2C9, the principal metabolizing enzyme of the coumarins, and VKORC1, the molecular target for coumarins, has strongly stimulated the research on pharmacogenetics of vitamin K antagonists, also designated as coumarins. From 1999 to 2004 a number of observational studies firmly established associations between being carrier of the CYP2C9*2 and especially the CYP2C9*3 allele and reduced coumarin dose requirements and increased risks of overanticoagulation and even major bleeding compared to CYP2C9 wild type patients. The identification of the VKORC1 gene in 2004 gave rise to more observational studies, which mostly indicated a larger contribution of variants of these gene to the interindividual variability in dose requirements. However, whereas overanticoagulation in the initial period of therapy appears to be associated with VKORC1 as well as CYP2C9 genotype, the CYP2C9 genotype could be a more important predictor for major bleeding and retarded stabilisation. The recent discovery that only one single nucleotide polymorphism in the VKORC1 gene, the -1639G>A polymorphism, is representative for VKORC1 activity and the recent conclusion from a genome-wide scan that VKORC1 and CYP2C9 are the only genes with relevant effects on coumarin response, seem to be definitive demarcations of the genetic information which could be needed for improvement of the existing coumarin dosing algorithms. The observational studies from the last decade provided valuable insights into the effects of genetic factors on variability in coumarin response. During the forthcoming years randomized clinical trials are needed to evaluate whether this genetic information will improve the benefit-risk ratio of coumarins.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1873-4286
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
187-203
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Pharmacogenetics of oral anticoagulant therapy.
pubmed:affiliation
Utrecht Institute for Pharmaceutical Sciences, Division of Pharmacoepidemiology and Pharmacotherapy, Utrecht, The Netherlands. t.schalekamp@uu.nl
pubmed:publicationType
Journal Article, Review