Polymorphisms of COX-1 and GP VI associate with the antiplatelet effect of aspirin in coronary artery disease patients

Aino Lepäntalo; Jussi Mikkelsson; Julio C. Reséndiz; Leena Viiri; Janne T. Backman; Esko Kankuri; Pekka J. Karhunen; Riitta Lassila

doi:10.1160/TH05-07-0516

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2006; 95(02): 253-259
DOI: 10.1160/TH05-07-0516

Platelets and Blood Cells

Schattauer GmbH

Polymorphisms of COX-1 and GP VI associate with the antiplatelet effect of aspirin in coronary artery disease patients

Aino Lepäntalo

¹Department of Internal Medicine, Helsinki University Central Hospital, Helsinki, Finland

,

Jussi Mikkelsson

²Research Unit, Laboratory Centre, Tampere University Hospital and Medical School, University of Tampere, Tampere, Finland

,

Julio C. Reséndiz

³Wihuri Research Institute, Helsinki, Finland

,

Leena Viiri

²Research Unit, Laboratory Centre, Tampere University Hospital and Medical School, University of Tampere, Tampere, Finland

,

Janne T. Backman

⁴Department of Clinical Pharmacology, University of Helsinki, Helsinki, Finland

,

Esko Kankuri

⁵Institute of Biomedicine, University of Helsinki, Helsinki, Finland

,

Pekka J. Karhunen

²Research Unit, Laboratory Centre, Tampere University Hospital and Medical School, University of Tampere, Tampere, Finland

,

Riitta Lassila

¹Department of Internal Medicine, Helsinki University Central Hospital, Helsinki, Finland

› Author Affiliations

Abstract

Summary

The antiplatelet effect of aspirin varies individually. This study evaluated whether the antiplatelet effect of aspirin associates with polymorphisms in the genes coding for cyclo-oxygenase-1 (COX-1) and several platelet glycoprotein (GP) receptors in patients with stable coronary artery disease (CAD). Blood samples were collected from 101 aspirin-treated (mean 100 mg/d) patients. Compliance to treatment was assessed by plasma salicylate measurement. Platelet functions were assessed by two methods: 1) Response to arachidonic acid (AA, 1.5 mmol/L in aggregometry, and 2) PFA-100, evaluating platelet activation under high shear stress in the presence of collagen and epinephrine (CEPI). Aspirin non-response was defined as: 1) slope steeper than 12%/min in AA-aggregations,and 2) by closure time shorter than 170 s in PFA-100. The methods used detected different individuals as being aspirin non-responders. Five and 21 patients, respectively, were non-responders according to AA-induced aggregation and PFA-100. Increased plasma thromboxane B₂ levels correlated with poor aspirin-response measured with both AA-induced aggregations and PFA-100 (P=0.02 and P=0.003, respectively). Of the non-responders detected by AA, 3 of5 (60%) carried the rareG allele for the -A842G polymorphism of COX-1 in contrast to 16 of 96 (17%) responders (P=0.016). Diabetes was associated with poor response. Aspirin non-response detected by PFA-100 associated with C13254T polymorphism of GP VI and female gender (P=0.012 and P=0.019, respectively). Although two patients were possibly non-compliant, this did not effect present conclusions. Evaluation of aspirin efficacy by AA-induced aggregation and PFA-100 detected different individuals, with different genotypic profiles, as being aspirin non-responders.

Keywords

Aspirin - cyclo-oxygenase-1 - genotype - glycoprotein VI - coronary artery disease

Full Text

References

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