title: Lack of association between gene sequence variations of platelet membrane receptors and aspirin responsiveness detected by the PFA-100 system in patients with coronary artery disease.
abstract: Platelet membrane receptors play a pivotal role in thrombus formation. Expression of platelet membrane receptors are under genetic control and gene sequence variations of receptors pivotal to thrombotic formation have been hypothesized to contribute to different degrees of individual response to aspirin. The aim of the present study was to investigate the impact of functional genetic polymorphisms of platelet membrane receptors on aspirin sensitivity assessed by means of the PFA-100 system in patients with coronary artery disease. Gene sequence variations of three platelet membrane receptors (GPIa/IIa, P2Y12, GPIIb/IIIa) pivotal to thrombus formation were assessed in 76 patients with coronary artery disease on chronic aspirin treatment. Patients with reduced sensitivity to aspirin were defined when closure-times of collagen/epinephrine cartridges < or =193 seconds and coined as PFA-100 non-responders. PFA-100 non-responders were observed in 33% of patients. Patients with diabetes mellitus were more frequently PFA-100 non-responders. Closure times of collagen/ADP coated cartridges were reduced in PFA-100 non-responders. The genotype distribution was similar in PFA-100 responder and non-responder patients for all three genotypes and did not vary in contemporaneous carriers of allelic variants. In conclusion, in vitro determined sensitivity to aspirin assessed using PFA-100 is not associated with gene sequence variations of platelet membrane receptors key to thrombus formation.
authors.affiliation: Cardiovascular Institute, San Carlos University Hospital, Madrid, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Bernardo
authors.forename: Dominick J
authors.initials: DJ
authors.lastname: Angiolillo
authors.forename: Celia
authors.initials: C
authors.lastname: Ramírez
authors.forename: Ugo
authors.initials: U
authors.lastname: Cavallari
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Trabetti
authors.forename: Manel
authors.initials: M
authors.lastname: Sabaté
authors.forename: Rosana
authors.initials: R
authors.lastname: Hernández
authors.forename: Raul
authors.initials: R
authors.lastname: Moreno
authors.forename: Javier
authors.initials: J
authors.lastname: Escaned
authors.forename: Fernando
authors.initials: F
authors.lastname: Alfonso
authors.forename: Camino
authors.initials: C
authors.lastname: Bañuelos
authors.forename: Marco A
authors.initials: MA
authors.lastname: Costa
authors.forename: Theodore A
authors.initials: TA
authors.lastname: Bass
authors.forename: Pier Franco
authors.initials: PF
authors.lastname: Pignatti
authors.forename: Carlos
authors.initials: C
authors.lastname: Macaya
authors.forename: Antonio
authors.initials: A
authors.lastname: Fernandez-Ortiz
mesh_terms: D000368:Aged; D001241:Aspirin / Q000008:administration & dosage*; D002908:Chronic Disease; D003324:Coronary Artery Disease / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010979:Platelet Function Tests / Q000295:instrumentation; D010980:Platelet Membrane Glycoproteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests
chemical_list: D005343:Fibrinolytic Agents; D010980:Platelet Membrane Glycoproteins; D001241:Aspirin