title: Evaluation of clopidogrel response variability and identification of the CYP2C19 polymorphism in Mexican patients.
abstract: OBJECTIVE
  Drug inhibition of platelet P2Y12 adenosine diphosphate receptor has reduced the incidence of adverse cardiovascular events after percutaneous coronary interventions. The analysis of the phosphorylation status of vasodilator-stimulated phosphoprotein by flow cytometry has shown a predictive value for adverse events and stent thrombosis. Polymorphisms of CYP2C19 in high risk patients may also relate to adverse cardiovascular events.
  
  
  METHODS
  Ninety patients were enrolled. Patients received a 600mg clopidogrel loading dose. Blood samples were obtained at the time of the procedure and 24h later, platelet reactivity was assessed by vasodilator-stimulated phosphoprotein phosphorylation measurement using flow cytometry. Low response to clopidogrel was defined as a platelet reactivity index≥50%. The presence of CYP2C19*2 was identified with the restriction enzyme SmaI.
  
  
  RESULTS
  Mean platelet reactivity index: 53.45±22.48% in the baseline sample and 57.14±23.08% at 24h (p=0.183); 40% of patients behaved as good responders, the rest behaved as non-responders with 38% of patients showing platelet reactivity indexes between 50-70% and 22% showing indexes above 70%. The CYP2C19*2 polymorphism was found in 17% of patients, with a 3.9% AA homozygous genotype carriers.
  
  
  CONCLUSIONS
  Response to the clopidogrel loading dose showed a wide variability among patients with 40% responding to the drug according to previously established cut-off values. Our results showed that 3.9% of patients show the AA genotype. To our knowledge, this is the first study involving clopidogrel response by flow citometry and genotype typification in Mexican Mestizo population.
authors.affiliation: División de Estudios de Posgrado, Facultad de Ciencias Médicas y Biológicas Dr. Ignacio Chávez, Universidad Michoacana de San Nicolás de Hidalgo, Morelia, Michoacán, Mexico. Electronic address: marthaevaviveros@yahoo.com.mx.
authors.forename: Martha Eva
authors.initials: ME
authors.lastname: Viveros
authors.affiliation: Servicio de Cardiología Intervencionista, Hospital General Dr. Miguel Silva, Morelia, Michoacán, Mexico.
authors.forename: Carlos
authors.initials: C
authors.lastname: Areán
authors.affiliation: División de Estudios de Posgrado, Facultad de Ciencias Médicas y Biológicas Dr. Ignacio Chávez, Universidad Michoacana de San Nicolás de Hidalgo, Morelia, Michoacán, Mexico.
authors.forename: Sergio
authors.initials: S
authors.lastname: Gutiérrez
authors.affiliation: División de Estudios de Posgrado, Facultad de Ciencias Médicas y Biológicas Dr. Ignacio Chávez, Universidad Michoacana de San Nicolás de Hidalgo, Morelia, Michoacán, Mexico.
authors.forename: Soledad
authors.initials: S
authors.lastname: Vázquez
authors.affiliation: Unidad de Investigación Dr. Mario Alvizouri, Hospital General Dr. Miguel Silva, Morelia, Michoacán, Mexico.
authors.forename: Mario Humberto
authors.initials: MH
authors.lastname: Cardiel
authors.affiliation: División de Estudios de Posgrado, Facultad de Ciencias Médicas y Biológicas Dr. Ignacio Chávez, Universidad Michoacana de San Nicolás de Hidalgo, Morelia, Michoacán, Mexico.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Taboada
authors.affiliation: División de Estudios de Posgrado, Facultad de Ciencias Médicas y Biológicas Dr. Ignacio Chávez, Universidad Michoacana de San Nicolás de Hidalgo, Morelia, Michoacán, Mexico.
authors.forename: Gissela
authors.initials: G
authors.lastname: Marín
authors.affiliation: Servicio de Cardiología Intervencionista, Hospital General Dr. Miguel Silva, Morelia, Michoacán, Mexico.
authors.forename: Ruben
authors.initials: R
authors.lastname: Solorio
authors.affiliation: División de Estudios de Posgrado, Facultad de Ciencias Médicas y Biológicas Dr. Ignacio Chávez, Universidad Michoacana de San Nicolás de Hidalgo, Morelia, Michoacán, Mexico.
authors.forename: Nalley
authors.initials: N
authors.lastname: García
mesh_terms: D000077144:Clopidogrel; D003430:Cross-Sectional Studies; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008800:Mexico; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine
keywords: Alta reactividad plaquetaria en tratamiento; Análisis VASP; CYP2C19*2 polymorphysm; Clopidogrel resistance; High on treatment platelet reactivity; Mexico; México; P2Y12; Polimorfismo CYP2C19*2; Receptor P2Y12; Resistencia a clopidogrel; VASP analysis