Linked Life Data

16878445

Source:http://linkedlifedata.com/resource/pubmed/id/16878445

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2006-8-1
pubmed:abstractText
Pharmacogenetics, a discipline still in its infancy, is the study of genetically determined variations in how individuals respond to drugs. Mutations may affect drug metabolism, transmembrane transport into cells, or target receptors. Genetic polymorphisms affecting drug metabolism were the first to be identified. Genetic factors control the activity of phase I reactions involving cytochrome (CYP) P450 isoenzymes. Three CYP families catalyze drug metabolism in humans. Their genes have been identified and polymorphisms have been described in various populations, leading to either high activity ("extensive metabolizer" phenotype) or low activity ("poor metabolizer" phenotype). The CYP2C9 polymorphism illustrates the potential clinical importance of pharmacogenetics. This enzyme catalyzes the metabolism of the coumarinic oral anticoagulants acenocoumarol and warfarin. The homozygous mutant genotype CYP 2C9 *31*3, present in 0, 7% of Caucasians, leads to low enzyme activity and thus to the accumulation of these drugs in the body; this in turn increases the anticoagulant activity and induces a higher risk of bleeding. In three clinical studies of patients and healthy volunteers, we found that this CYP2C9 *3 mutant allele was responsible for 14% of the variability in the response to these drugs. Then, by studying the genetic polymorphism of the receptor site of oral anticoagulants--the vitamin K epoxide reductase multiprotein complex--we showed that a combination of the two genetic variants (CYP2C9 and the receptor site) was responsible for 50% of the variability. These data suggest that patients who have both genetic polymorphisms could be at an increased risk of bleeding during oral anticoagulant therapy.
pubmed:language
fre
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0001-4079
pubmed:author
pubmed:issnType
Print
pubmed:volume
190
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
37-49; discussion 50-3
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
[Pharmacogenetics and interindividual variability in drug response: cytochrome P-450 2C9 and coumarin anticoagulants].
pubmed:affiliation
Service de Pharmacologie, Faculté de Médecine Pierre et Marie Curie (St-Antoine)-Université Paris.
pubmed:publicationType
Journal Article, English Abstract