Document Detail


Effect of paraoxonase-1 polymorphism on clinical outcomes in patients treated with clopidogrel after an acute myocardial infarction.
MedLine Citation:
PMID:  21918510     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Paraoxonase-1 (PON1) Q192R polymorphism was recently suggested to determine per se clopidogrel response on major cardiovascular events (MACEs). We assessed the impact of PON1, CYP2C19, and ABCB1 polymorphisms on MACE in clopidogrel-treated acute myocardial infarction (AMI) patients (N = 2,210), including those undergoing percutaneous coronary intervention (PCI) (n = 1,538). PON1 polymorphism was not associated with increased risk of in-hospital death and MACEs at 1 year (adjusted hazard ratio (HR) 1.03, 95% confidence interval (CI) 0.66-1.61 and adjusted HR 0.77, 95% CI 0.42-1.41 for QQ versus RR in all and PCI patients, respectively). The presence of two CYP2C19 loss-of-function (LOF) alleles was associated with the risk of in-hospital death and MACEs at 1 year in the overall population (adjusted odds ratio (OR) 3.67, 95% CI 1.05-12.80 and adjusted HR 1.96, 95% CI 1.08-3.54) and in PCI patients (adjusted OR 6.87, 95% CI 2.52-18.72 and adjusted HR 3.06, 95% CI 1.47-6.41). Unlike CYP2C19 polymorphism, PON1 (Q192R) polymorphism is not a major pharmacogenetic contributor of clinical response to clopidogrel in AMI patients.
Authors:
T Simon; P G Steg; L Becquemont; C Verstuyft; S Kotti; F Schiele; E Ferrari; E Drouet; G Grollier; N Danchin
Publication Detail:
Type:  Comparative Study; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't     Date:  2011-09-14
Journal Detail:
Title:  Clinical pharmacology and therapeutics     Volume:  90     ISSN:  1532-6535     ISO Abbreviation:  Clin. Pharmacol. Ther.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-09-21     Completed Date:  2011-11-23     Revised Date:  2011-12-23    
Medline Journal Info:
Nlm Unique ID:  0372741     Medline TA:  Clin Pharmacol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  561-7     Citation Subset:  AIM; IM    
Affiliation:
Assistance Publique-Hôpitaux de Paris (APHP), Hôpital St. Antoine, URC-EST, Paris, France. tabassome.simon@sat.aphp.fr
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MeSH Terms
Descriptor/Qualifier:
Aged
Aged, 80 and over
Aryldialkylphosphatase / genetics*
Female
Follow-Up Studies
Genotype
Hospital Mortality / trends
Humans
Male
Middle Aged
Myocardial Infarction / drug therapy*,  genetics*,  mortality
Polymorphism, Genetic / genetics*
Prospective Studies
Registries
Ticlopidine / analogs & derivatives*,  therapeutic use
Treatment Outcome
Chemical
Reg. No./Substance:
55142-85-3/Ticlopidine; 90055-48-4/clopidogrel; EC 3.1.8.1/Aryldialkylphosphatase; EC 3.1.8.1/PON1 protein, human
Comments/Corrections
Comment In:
Clin Pharmacol Ther. 2011 Dec;90(6):771-4   [PMID:  22089342 ]
Clin Pharmacol Ther. 2011 Dec;90(6):774-6   [PMID:  22089343 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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