Effect of paraoxonase-1 polymorphism on clinical outcomes in patients treated with clopidogrel after an acute myocardial infarction.

Abstract

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
• Journal: Clinical pharmacology and therapeutics (Clin Pharmacol Ther) Vol. 90 Issue 4 Pg. 561-7 (Oct 2011) ISSN: 1532-6535 [Electronic] United States
• PMID: 21918510 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Clopidogrel
• Aryldialkylphosphatase
• PON1 protein, human
• Ticlopidine

Topics

• Aged
• Aged, 80 and over
• Aryldialkylphosphatase (genetics)
• Clopidogrel
• 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