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Role of platelet glycoprotein polymorphisms in cardiovascular diseases

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Abstract

Atherothrombosis is the leading cause of death in western countries. Major complications of atherothrombotic disease, which are responsible for a large burden of morbidity and mortality, are acute coronary syndromes, ischemic stroke, and peripheral occlusive disease. Plaque rupture, platelet adhesion, aggregation, and thrombosis may lead to unstable angina and may progress to myocardial infarction as well as to ischemic stroke. Platelet membrane glycoprotein receptors mediate crucial reactions in acute thrombosis and chronic processes of atherogenesis. The platelet glycoprotein GP IIb/IIIa, which is the most abundant platelet receptor, also represents the drug target of a novel class of anti-platelet drugs, which includes abciximab, tirofiban, and eptifibatide. The genes encoding the three major platelet glycoprotein receptors (GP Ib/IX/V, GP Ia/IIa, and GP IIb/IIIa) are subject to considerable genetic variability. This paper reviews how polymorphisms in the platelet glycoprotein receptors affect platelet function, susceptibility to atherothrombosis and its major complications including myocardial infarction, stroke, and complications following percutaneous coronary interventions, and individual variability of drug response. Recent data on platelet glycoprotein receptor polymorphisms as modifiers of drug action and as predictors of drug response offer the perspective of individualized drug treatment. Prospective studies will show whether this approach is useful or not. As the data reviewed here show clearly, future clinical trials should routinely take into account genetic susceptibility factors and modifiers, both for study design and for predefined patient stratification.

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Abbreviations

ACS:

Acute coronary syndrome

CI:

Confidence interval

DCA:

Directional coronary atherectomy

GP:

Glycoprotein

MACE:

Major adverse cardiac event

MI:

Myocardial infarction

PCI:

Percutaneous coronary intervention

PTCA:

Percutaneous transluminal coronary angioplasty

RR:

Relative risk

SCD:

Sudden cardiac death

VWF:

Von Willebrand factor

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Acknowledgements

This work was supported by the German Ministry of Education, and Research “Berlin Center for Genome Based Bioinformatics” grant 031U209B the “Lead Project Partnership: Pharmacogenetic Diagnostics” grant 01 GG 9845/5, and a grant from the US National Institutes of Health (Grant RO1 HL65205).

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Authors and Affiliations

  1. Institute of Clinical Pharmacology, Charité University Medical Center, Humboldt University of Berlin, Campus Mitte, Schumannstrasse 20–21, Berlin, Germany

    Christian Meisel

  2. Departments of Medicine and Molecular and Human Genetics, Baylor College of Medicine and Veterans Affairs Medical Center, Houston, Texas, USA

    José A. López

  3. Department of Cardiology, Charité University Medical Center, Humboldt University of Berlin, Campus Mitte, Schumannstrasse 20–21, Berlin, Germany

    Karl Stangl

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  1. Christian Meisel
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  2. José A. López
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Correspondence to Christian Meisel.

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Meisel, C., López, J.A. & Stangl, K. Role of platelet glycoprotein polymorphisms in cardiovascular diseases. Naunyn-Schmiedeberg's Arch Pharmacol 369, 38–54 (2004). https://doi.org/10.1007/s00210-003-0828-y

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