Cytochrome P450 2C19 loss-of-function polymorphism, but not CYP3A4 IVS10+12G/A and P2Y12 T744C polymorphisms, is associated with response variability to dual antiplatelet treatment in high-risk vascular patients

Betti Giusti, Anna Maria Gori, Rossella Marcucci, Claudia Saracini, Ilaria Sestini, Rita Paniccia, Serafina Valente, Davide Antoniucci, Rosanna Abbate, Gian Franco Gensini

Research output: Contribution to journalArticlepeer-review

Abstract

OBJECTIVES: The aim of this study was to evaluate the effect of polymorphisms affecting the clopidogrel metabolism (CYP3A4 IVS10+12G/A and CYP2C19*2) and the P2Y12 receptor (P2Y12 T744C) on modulating platelet function in acute coronary syndrome patients on dual antiplatelet treatment. BACKGROUND: Residual platelet reactivity (RPR) phenomenon on antiplatelet therapy requires clarification. P2Y12 T744C, CYP3A4 IVS10+12G/A and, in healthy individuals only, CYP2C19*2 polymorphisms have been investigated; however, the influence on platelet reactivity in a large population of high-risk vascular patients on dual antiplatelet treatment has not yet been elucidated. METHODS: A total of 1419 acute coronary syndrome patients on dual antiplatelet treatment were studied. Platelet function was evaluated by platelet-rich plasma aggregation. Electronic nanochips and restriction-fragment length polymorphism were used for analysis of polymorphisms. RESULTS: Only CYP2C19*2, out of the three investigated polymorphisms, is associated with higher platelet reactivity. Carriers of the *2 allele had significantly higher platelet aggregation values after arachidonic acid (AA; P=0.043), 2 μmol/l adenosine 5′ diphosphate (ADP; P

Original languageEnglish
Pages (from-to)1057-1064
Number of pages8
JournalPharmacogenetics and Genomics
Volume17
Issue number12
DOIs
Publication statusPublished - Dec 2007

Keywords

  • Acute coronary syndrome
  • ADP receptor P2Y
  • Cytochrome P450
  • Dual antiplatelet treatment
  • Pharmacogenetics
  • Polymorphism
  • Residual platelet reactivity

ASJC Scopus subject areas

  • Genetics
  • Pharmacology

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