Linked Life Data

16772608

Source:http://linkedlifedata.com/resource/pubmed/id/16772608

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2006-9-21
pubmed:abstractText
The capacity of clopidogrel to inhibit ADP-induced platelet aggregation shows wide intersubject variability. To determine whether frequent functional variants of genes coding for candidate cytochrome P450 (CYP) isoenzymes involved in clopidogrel metabolic activation (CYP2C19*2, CYP2B6*5, CYP1A2*1F, and CYP3A5*3 variants) influence the platelet responsiveness to clopidogrel, we conducted a prospective pharmacogenetic study in 28 healthy white male volunteers treated for 7 days with clopidogrel 75 mg/d. We observed that pharmacodynamic response to clopidogrel was significantly associated with the CYP2C19 genotype. Twenty of the subjects were wild-type CYP2C19 (*1/*1) homozygotes, while the other 8 subjects were heterozygous for the loss-of-function polymorphism CYP2C19*2 (*1/*2). Baseline platelet activity was not influenced by the CYP2C19 genotype. In contrast, platelet aggregation in the presence of 10 muM ADP decreased gradually during treatment with clopidogrel 75 mg once daily in *1/*1 subjects, reaching 48.9% +/- 14.9% on day 7 (P < .001 vs baseline), whereas it did not change in *1/*2 subjects (71.8% +/- 14.6% on day 7, P = .22 vs baseline, and P < .003 vs *1/*1 subjects). Similar results were found with VASP phosphorylation. The CYP2C19*2 loss-of-function allele is associated with a marked decrease in platelet responsiveness to clopidogrel in young healthy male volunteers and may therefore be an important genetic contributor to clopidogrel resistance in the clinical setting.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
108
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2244-7
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Cytochrome P450 2C19 loss-of-function polymorphism is a major determinant of clopidogrel responsiveness in healthy subjects.
pubmed:affiliation
INSERM U 765, Service d'Hématologie Biologique A, Hôpital Européen Georges Pompidou, 20 rue Leblanc, 75908 Paris Cedex 15, France. pascale.gaussem@egp.aphp.fr
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't