Lack of association between aspirin responsiveness and seven candidate gene haplotypes in patients with symptomatic vascular disease

Thomas J. Kunicki; Shirley A. Williams; Diane J. Nugent; Paul Harrison; Helen C. Segal; Anila Syed; Peter M. Rothwell

doi:10.1160/TH08-05-0287

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2009; 101(01): 123-133
DOI: 10.1160/TH08-05-0287

Platelets and Blood Cells

Schattauer GmbH

Lack of association between aspirin responsiveness and seven candidate gene haplotypes in patients with symptomatic vascular disease

Thomas J. Kunicki

¹Division of Experimental Hemostasis and Thrombosis, of the Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA

,

Shirley A. Williams

²Division of Hematology, The Children’s Hospital of Orange County, Orange, California, USA

,

Diane J. Nugent

²Division of Hematology, The Children’s Hospital of Orange County, Orange, California, USA

,

Paul Harrison

³Oxford Haemophilia and Thrombosis Centre, Churchill Hospital, Oxford, UK

,

Helen C. Segal

³Oxford Haemophilia and Thrombosis Centre, Churchill Hospital, Oxford, UK

,

Anila Syed

⁴Stroke Prevention Research Unit, Department of Clinical Neurology, University of Oxford, Oxford, UK

,

Peter M. Rothwell

⁵University Department of Clinical Neurology, Radcliffe Infirmary, Oxford, UK

› Author Affiliations

Abstract

Summary

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 α2β1and αIIbβ3 (ITGA2, ITGA2B, and ITGB3), platelet glycoproteins Ibα 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.

Keywords

Aspirin - PFA-100 - platelet - SNP - VWF

Full Text

References

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