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, Inhaltsverzeichnis

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

Autoren

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

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

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Referenzen

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