title: Lack of association between aspirin responsiveness and seven candidate gene haplotypes in patients with symptomatic vascular disease.
abstract: We studied the effect of prophylactic aspirin (ASA) ingestion on platelet function in 463 patients with stroke, transient ischemic attack (TIA) or acute coronary disease (ACD), using the Platelet Function Analyzer-100 (PFA-100). We correlated ASA responsiveness with haplotypes of seven candidate genes, selected for their documented role in platelet function, namely, the genes for integrins alpha2beta1and alphaIIbbeta3 (ITGA2, ITGA2B, and ITGB3), platelet glycoproteins Ibalpha and VI (GPIBA and GP6), the purinergic receptor P2Y1 (P2RY1), and prostaglandin H synthase 1 (PTGS1 = COX1). Non-responsiveness to ASA was defined as the failure of prior ASA ingestion to prolong the PFA-100 closure time (CT) when blood was perfused through cartridges coated with collagen plus epinephrine (CEPI-CT). ASA non-responsiveness was observed in 114 of 463 patients (24.6 %), but was not associated with haplotypes of any of the seven candidate genes. There was also no association between any haplotypes and the CT when blood was perfused through cartridges coated with collagen plus ADP (CADP-CT). The ASA non-responsive cohort had significantly increased whole blood platelet counts (p = 0.03) and plasma von Willebrand Factor antigen levels (p < 0.001), which likely contributes to resistance to the inhibitory effects of ASA in the PFA-100.
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. tomk@scripps.edu
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Kunicki
authors.forename: Shirley A
authors.initials: SA
authors.lastname: Williams
authors.forename: Diane J
authors.initials: DJ
authors.lastname: Nugent
authors.forename: Paul
authors.initials: P
authors.lastname: Harrison
authors.forename: Helen C
authors.initials: HC
authors.lastname: Segal
authors.forename: Anila
authors.initials: A
authors.lastname: Syed
authors.forename: Peter M
authors.initials: PM
authors.lastname: Rothwell
mesh_terms: D000244:Adenosine Diphosphate; D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000627:therapeutic use*; D015331:Cohort Studies; D051545:Cyclooxygenase 1 / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics*; D004739:England; D004837:Epinephrine; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D039421:Integrin alpha2 / Q000235:genetics; D039661:Integrin beta3 / Q000235:genetics; D008297:Male; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects* / Q000235:genetics; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010976:Platelet Count; D010979:Platelet Function Tests / Q000295:instrumentation; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D018048:Receptors, Purinergic P2 / Q000235:genetics; D017211:Treatment Failure; D015854:Up-Regulation; D014652:Vascular Diseases / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: C056564:ITGA2B protein, human; C061248:ITGB3 protein, human; D039421:Integrin alpha2; D039661:Integrin beta3; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D010975:Platelet Aggregation Inhibitors; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; D018048:Receptors, Purinergic P2; C094990:adhesion receptor; C098341:platelet membrane glycoprotein VI; D014841:von Willebrand Factor; D000244:Adenosine Diphosphate; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; D001241:Aspirin; D004837:Epinephrine