Cytochrome P450 CYP 2C19*2 Associated with Adverse 1-Year Cardiovascular Events in Patients with Acute Coronary Syndrome

PLoS One. 2015 Jul 6;10(7):e0132561. doi: 10.1371/journal.pone.0132561. eCollection 2015.

Abstract

Background: The cytochrome P450 (CYP450) 2C19 681 genotypes affect the antiplatelet activity of clopidogrel. We investigated the correlation of CYP 2C19 681G > A mutation with clopidogrel resistance (CR). Additionally, we studied the effect of CR on clinical prognosis of patients with acute coronary syndrome (ACS).

Methods: One hundred ten ACS patients undergoing percutaneous coronary intervention, who were followed-up for 1 year, were included in the study. The patients were co-administered aspirin 100 mg/d and clopidogrel 75mg/d following a loading dose of 300 mg. CR was assessed on the basis of polymorphism observed in the CYP2C19 subgroup.

Results: Patients in GG genotype group exhibited greater inhibition of platelet aggregation than patients in GA and AA genotype groups (16.2 ± 10.1%; 10.2 ± 9.9%; 8.0 ± 5.9%, respectively, p < 0.01). CYP2C19 681GG genotype group was associated with lower CR than CYP2C19 681A allele (GA + AA) group (9/59 vs. (12+5)/51; p = 0.009). Over a follow-up of 12 months, the incidence of recurrent angina, acute myocardial infarction, and intra-stent thrombosis in CYP2C19 681 GG carriers was significantly lower than that in CYP2C19 681A allele (GA + AA) group (2/59 vs. 8/51, 1/59 vs. 6/51, 0 vs. 4/51, respectively, p < 0.05).

Conclusion: CYP 2C19*2 is associated with reduced clopidogrel antiplatelet activity and might be an important marker for poor prognosis of ACS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activation, Metabolic / genetics
  • Acute Coronary Syndrome / drug therapy
  • Acute Coronary Syndrome / genetics*
  • Acute Coronary Syndrome / surgery
  • Aged
  • Alleles
  • Angina Pectoris / epidemiology
  • Angina Pectoris / genetics
  • Aspirin / therapeutic use
  • Clopidogrel
  • Coronary Restenosis / epidemiology
  • Coronary Restenosis / genetics
  • Coronary Thrombosis / epidemiology
  • Coronary Thrombosis / genetics
  • Cytochrome P-450 CYP2C19 / genetics*
  • Cytochrome P-450 CYP2C19 / physiology
  • Drug Resistance / genetics*
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Myocardial Infarction / epidemiology
  • Myocardial Infarction / genetics
  • Percutaneous Coronary Intervention
  • Platelet Aggregation Inhibitors / pharmacokinetics*
  • Platelet Aggregation Inhibitors / therapeutic use
  • Polymorphism, Single Nucleotide*
  • Prodrugs / pharmacokinetics*
  • Prodrugs / therapeutic use
  • Prognosis
  • Prospective Studies
  • Recurrence
  • Stents
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / pharmacokinetics
  • Ticlopidine / therapeutic use
  • Treatment Outcome

Substances

  • Platelet Aggregation Inhibitors
  • Prodrugs
  • Clopidogrel
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Ticlopidine
  • Aspirin

Grants and funding

This work was supported by grants from the Key Project of Natural Science Research of Anhui Province College (kj2011A263), Anhui, China, HC.