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PHARMACOGENETICS

Glycoprotein IIIA Gene (PlA) Polymorphism and Aspirin Resistance: Is There Any Correlation?

Assistant Professor, First Department of Medicine, School of Medicine, University of Pecs, Pecs, Hungary

Viktoria Havasi, MD, PhD

Candidate, Department of Medical Genetics and Child Development, School of Medicine, University of Pecs

Judit Bene, PhD

Candidate, Department of Medical Genetics and Child Development, School of Medicine, University of Pecs; Hungarian Academy of Science Clinical Genetic Research Group, Pecs

Katalin Komlosi, MD, PhD

Candidate, Department of Medical Genetics and Child Development, School of Medicine, University of Pecs

Laszlo Czopf, MD PhD

Associate Professor, First Department of Medicine, School of Medicine, University of Pecs

Eva Magyar, MD

Resident, First Department of Medicine, School of Medicine, University of Pecs

Csaba Feher, MD

Resident, First Department of Medicine, School of Medicine, University of Pecs

Gergely Feher, MD, PhD

Candidate, First Department of Medicine, School of Medicine, University of Pecs

Beata Horvath, MD PhD

Resident, First Department of Medicine, School of Medicine, University of Pecs

Zsolt Marton, MD PhD

Resident, First Department of Medicine, School of Medicine, University of Pecs

Tamas Alexy, MD, PhD

Candidate, First Department of Medicine, School of Medicine, University of Pecs

Tamas Habon, MD PhD

Associate Professor, First Department of Medicine, School of Medicine, University of Pecs

Levente Szabo

Statistician, First Department of Medicine, School of Medicine, University of Pecs

Kalman Toth, MD DSc

Head of Department, Vice Dean, First Department of Medicine, School of Medicine, University of Pecs

Bela Melegh, MD DSc

Co-Chair, Vice Dean, Department of Medical Genetics and Child Development, School of Medicine, University of Pecs

Reprints: Dr. Papp, First Department of Medicine, School of Medicine, University of Pecs, Ifjusag u. 13. H-7624, Pecs, Hungary, fax 36-72-536-148, elod.papp{at}aok.pte.hu

BACKGROUND: Platelet glycoprotein (GP) IIb/IIIa receptors play an inevitable role in platelet aggregation. The GP IIIa gene is polymorphic (PlA1/PlA2) and the presence of a PlA2 allele might be associated with an increased risk for acute coronary syndrome (ACS).

OBJECTIVE: To examine the prevalence of the PlA2 allele in patients with ACS and in subjects with or without aspirin resistance.

METHODS: The prevalence of the PlA2 allele was assessed in 158 patients with ACS and PlA2 compared with its prevalence in 199 healthy volunteers. The antiplatelet efficacy of aspirin was examined in all patients with ACS, as well as in 69 individuals who had suffered ischemic stroke and in 58 high-risk subjects without any known ischemic vascular events.

RESULTS: PlA2 prevalence was significantly higher in patients with ACS (59/158) than in the control group (51/199; p < 0.05). Carriers of the PlA2 allele had a significantly higher risk of developing ACS, even after an adjustment to the risk factors (OR 5.74; 95% CI 1.75 to 18.8; p = 0.004). The occurrence of the PlA2 allele was significantly higher among patients with aspirin resistance than in subjects who demonstrated an appropriate response to the drug (allele frequencies, 0.21 vs 0.14; p < 0.05). All patients homozygous for the PlA2 allele had an inadequate platelet response to aspirin.

CONCLUSIONS: Our results support the hypothesis that carriers of the PlA2 allele might have an increased risk for ACS. PlA2 homozygosity was associated with an inadequate response to aspirin therapy. Our data further suggest that patients with PlA2 allele homozygosity might benefit from antiplatelet therapy based on adenosine diphosphate antagonists throughout secondary treatment for prevention of ACS.

Key Words: aspirin resistance, PlA polymorphism

Published Online, April 19, 2005. www.theannals.com, DOI 10.1345/aph.1E227

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