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CLINICAL STUDY

Role of Kozak sequence polymorphism of platelet glycoprotein Ib as a risk factor for coronary artery disease and catheter interventions

Christian Meisel, MD^*, Vahid Afshar-Kharghan, MD, Ingolf Cascorbi, MD, PhD^*, Michael Laule, MD, Verena Stangl, MD, Stefan B. Felix, MD, Gert Baumann, MD, José A. López, MD, Ivar Roots, MD^* and Karl Stangl, MD

^* Institute of Clinical Pharmacology, Berlin, Germany
Department of Cardiology, Charité University Medical Center, Campus Mitte, Humboldt University of Berlin, Berlin, Germany
Departments of Medicine and Molecular and Human Genetics, Baylor College of Medicine and Veterans Affairs Medical Center, Houston, Texas, USA

Manuscript received October 12, 2000; revised manuscript received April 16, 2001, accepted June 14, 2001.

Reprint requests and correspondence: Dr. Karl Stangl, Medizinische Klinik und Poliklinik, Kardiologie, Angiologie und Pneumologie, Universitätsklinikum Charité, Campus Mitte, Humboldt-Universität zu Berlin, D-10098 Berlin, Germany
karl.stangl{at}charite.de

OBJECTIVES

We sought to determine the role of the –5T/C polymorphism of the platelet glycoprotein (GP) Ib as a potential risk factor for coronary artery disease (CAD) and adverse events complicating a coronary catheter intervention.

BACKGROUND

The platelet GP Ib-IX-V receptor complex plays a crucial role in arterial thrombus formation. The –5T/C polymorphism of GP Ib is associated with increased receptor density.

METHODS

We genotyped 1,000 patients with angiographically confirmed CAD, as well as 1,000 age- and gender-matched control subjects, for this polymorphism by polymerase chain reaction/restriction fragment length polymorphism. Among the patients with CAD, 269 underwent percutaneous transluminal coronary angioplasty (PTCA), 103 underwent directional coronary atherectomy and 278 underwent stenting. This intervention group was followed for a 30-day composite end point of target vessel revascularization, myocardial infarction or death.

RESULTS

Carriers of the –5C allele were significantly over-represented in the group of patients developing acute coronary syndromes (relative risk [RR] 1.43, 95% confidence interval [CI] 1.05 to 1.95, p = 0.02). The –5C allele furthermore predicted an increased risk for developing complications after PTCA (RR 3.75, 95% CI 1.15 to 12.27, p = 0.029).

CONCLUSIONS

The –5C allele of the GP Ib Kozak polymorphism may represent a risk factor in clinical conditions in which thrombosis plays an important role, such as in acute coronary syndromes and in complications after PTCA.

Abbreviations and Acronyms   CAD = coronary artery disease   CI = confidence interval   CRP = C-reactive protein   DCA = directional coronary atherectomy   GP = glycoprotein   PAI-1 = plasminogen activator inhibitor-1   PTCA = percutaneous transluminal coronary angioplasty   RR = relative risk   vWF = von Willebrand factor

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