title: The impact of CYP3A5*1/*3, PIA1/A2 and T744C polymorphisms on clopidogrel and acetylsalicylic acid response variability in Mexican population.
abstract: BACKGROUND
  Clopidogrel is recommended in addition to aspirin to prevent atherothrombotic events in patients with acute coronary syndromes (ACS) and in those undergoing percutaneous coronary intervention (PCI). However, an interindividual variability in platelet inhibition response to clopidogrel has been demonstrated, and is associated with recurrent cardiovascular events. Multiple mechanisms have been associated with no response including genetics factors.
  
  
  METHODS
  The present study enrolled 60 patients with ACS undergoing emergent PCI. Platelet aggregation to adenosine diphosphate and arachidonic acid was assessed by turbidimetric method at 24 hours after dual administration of 300 mg of clopidogrel and 300 mg of acetylsalicylic acid loading dose. Clopidogrel or acetylsalicylic acid resistance was defined by persistence of Platelet Reactivity (PR=ADP-Ag >70% or PR=Arachidonic Acid-Ag>20%) respectively. The CYP3A51*/5*, PIA1/A2, and T744C polymorphisms were determined in all participants by PCR-RFLP.
  
  
  RESULTS
  The allelic frequencies were: CYP3A5*3 (71.65%), PIA2 (10.8%), and 744 C (15.0%). We founded high percent of clopidogrel resistance (60.0%), compared with 8.3% of acetylsalicylic acid in those patients. The genotype frequencies of those polymorphisms were similar between responders and non responders defined by PR. There was a high percent of coronary adverse events.
  
  
  CONCLUSIONS
  We identified a high percent of clopidogrel resistance in Mexican patients with ACS undergoing PCI. However, a normal platelet response to acetylsalicylic acid was observed in most of them. There was no association between CYP3A5*1/*3, PIA1/A2, and T744C polymorphisms and clopidogrel resistance. More studies are needed to determine the possible interaction between genetics factors, platelet response to clopidogrel and cardiovascular adverse events.
authors: Unidad de Investigación Médica en Trombosis, Hemostasia y Aterogénesis, H.G.R. No 1. Dr. "Carlos Mac Gregor Sánchez Navarro" Instituto Mexicano del Seguro Social, México DF, México. irmaisordia@yahoo.com.mx
authors: Irma
authors: I
authors: Isordia-Salas
authors: Marcos Jaciel
authors: MJ
authors: Olalde-Román
authors: David
authors: D
authors: Santiago-Germán
authors: Norma Corona
authors: NC
authors: de la Peña
authors: Jesús Salvador
authors: JS
authors: Valencia-Sánchez
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000453:epidemiology* / Q000601:surgery; D001241:Aspirin / Q000627:therapeutic use*; D000077144:Clopidogrel; D015897:Comorbidity; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D008297:Male; D008800:Mexico / Q000453:epidemiology; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015995:Prevalence; D058925:Receptors, Purinergic P2Y12 / Q000235:genetics; D012307:Risk Factors; D013927:Thrombosis / Q000453:epidemiology / Q000517:prevention & control; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D058925:Receptors, Purinergic P2Y12; D000077144:Clopidogrel; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D013988:Ticlopidine; D001241:Aspirin