title: C3435T polymorphism of the ABCB1 gene is associated with poor clopidogrel responsiveness in a Mexican population undergoing percutaneous coronary intervention.
abstract: BACKGROUND
  Clopidogrel is a pro-drug and its intestinal absorption is limited by the P-glycoprotein encoded by the ABCB1 gene. It is metabolized hepatically by cytochrome P450 enzymes encoded by CYP genes to produce an active metabolite that antagonizes the P2Y12 platelet receptor. Some patients exhibit poor clopidogrel responsiveness due to polymorphisms, resulting in thrombotic events. The aim of this study was to determine the relationship between poor clopidogrel responsiveness and the ABCB1, CYP and P2RY12 gene polymorphisms among patients undergoing percutaneous coronary intervention (PCI).
  
  
  RESULTS
  Two hundred seventy-six patients who underwent PCI were included in this study. Clopidogrel responsiveness was determined via optical aggregometry in platelet-rich plasma using 10 μM ADP. Patients exhibiting a platelet aggregation response higher than 70% were classified as poor responders. The genetic polymorphisms were analyzed via real-time PCR. Poor responsiveness to clopidogrel was noted in 22.1% of the patients. The TT genotype of the C3435T polymorphism of the ABCB1 gene and omeprazole usage were each associated with poor clopidogrel responsiveness (Exp (β) 2.73, p=0.009 and Exp (β) 3.86, p=0.04, respectively).
  
  
  CONCLUSIONS
  Poor clopidogrel responsiveness is associated with the TT genotype of the C3435T polymorphism of the ABCB1 gene.
authors.affiliation: Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, México, D.F., Mexico.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Calderón-Cruz
authors.affiliation: Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, México, D.F., Mexico.
authors.forename: Karen
authors.initials: K
authors.lastname: Rodríguez-Galván
authors.affiliation: Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, México, D.F., Mexico.
authors.forename: Luis Antonio
authors.initials: LA
authors.lastname: Manzo-Francisco
authors.affiliation: Departamento de Biología Molecular, Instituto Nacional de Cardiología, México D.F., Mexico.
authors.forename: Gilberto
authors.initials: G
authors.lastname: Vargas-Alarcón
authors.affiliation: Departamento de Biología Molecular, Instituto Nacional de Cardiología, México D.F., Mexico.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Fragoso
authors.affiliation: Departamento de Hemodinámica, Instituto Nacional de Cardiología México D.F., Mexico.
authors.forename: Marco Antonio
authors.initials: MA
authors.lastname: Peña-Duque
authors.affiliation: Departamento de Hemodinámica, Instituto Nacional de Cardiología México D.F., Mexico.
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Reyes-Gómez
authors.affiliation: Departamento de Hemodinámica, Instituto Nacional de Cardiología México D.F., Mexico.
authors.forename: Marco Antonio
authors.initials: MA
authors.lastname: Martínez-Ríos
authors.affiliation: Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, México, D.F., Mexico; Departamento de Biología Molecular, Instituto Nacional de Cardiología, México D.F., Mexico. Electronic address: aurorade2002@yahoo.com.
authors.forename: Aurora
authors.initials: A
authors.lastname: De la Peña-Díaz
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D000077144:Clopidogrel; D005260:Female; D006801:Humans; D008297:Male; D008800:Mexico; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention / Q000379:methods*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine
keywords: ABCB1; Polymorphisms; Poor clopidogrel responsiveness