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Platelet receptor gain-of-function single nucleotide polymorphisms in carotid and vertebral stenosis patients

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Abstract

The role of platelet receptor gain-of-function single nucleotide polymorphisms (SNP) in cardiovascular disease is controversial. We hypothesised that certain SNPs may accelerate the development of carotid artery stenosis. The intronic PAR-1 receptor intervening sequence-14 A/T (IVSn-14 A/T) polymorphism and three additional platelet receptor polymorphisms, i.e. GPIa (807C/T), GPIbα (5T/C) and HPA-1a/HPA-1b (Pl (A1/A2)) of GPIIIa were studied. The interaction of SNPs with conventional risk factors including male gender, hypertension, high cholesterol, diabetes, advanced age and smoking were investigated. The hypothesis was tested in 114 well-characterised patients with symptomatic carotid or vertebral stenosis from the British CAVATAS population and compared the results with 97 unrelated controls. The allele frequency of the platelet gain-of-function SNP was not significantly different in the CAVATAS population as compared to controls (PAR-1A/T (P = 0.13), GPIa C/T (P = 0.25), GPIIIa HPA-1a/HPA-1b (PlA1/A2) (P = 0.66) and GPIb T/C (P = 0.20)). In the subgroup of smokers, however, the prothrombotic GPIbα C mutated allele was found in a significantly higher frequency in the patient as compared to the control group (P = 0.04). Contrary to the primary hypothesis, the PAR-1A/T SNP as well as the other SNPs tested were not over- or underrepresented in the CAVATAS population. However, a significantly increased prevalence of GPIb-α (5C/T) was found in the subgroup of smokers and may represent an important cofactor in this patient group of our hypothesis-generating study.

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Acknowledgments

The authors would like to thank Prof. Jürg Hüsler and Niki Zumbrunnen, University of Berne (Switzerland) for statistical analysis, Dr. Luca Pontiggia for technical support and Mrs Allison Dwileski for editing the manuscript. This work was supported by the Swiss National Foundation (Grant Nr. 32-59449.99 and 3200-068228.02 to J.H. Beer) and by the KARDIO Foundation Baden (to J.H. Beer), Switzerland. CAVATAS was funded by grants from the British Heart Foundation, the NHS Management Executive and the Stroke Association. The ultrasound laboratory at the central office was funded by the Wellcome Trust and the Neurosciences Research Foundation. MMB’s Chair in Stroke Medicine at University College London is supported by the Reta Lila Weston Trust for Medical Research. Dr Lucy Coward and Ms Diane Thompson were responsible for patient recruitment and blood sampling, with support from Professor Graham Venables.

Conflict of interest

The authors have no conflicts of interest to declare.

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Authors and Affiliations

  1. Department of Medicine, Cantonal Hospital Baden, 5404, Baden, Switzerland

    Andrea Kopp Lugli, Linda Büchi, Marc Forestier & Juerg H. Beer

  2. Department of Anesthesia, University Hospital, Basel, Switzerland

    Andrea Kopp Lugli

  3. Stroke Research Group, University College of London Institute of Neurology, London, UK

    Martin M. Brown

  4. Department of Cardiology, University Hospital, Zurich, Switzerland

    Jan Steffel

  5. Hoffmann-La Roche, Basel, Switzerland

    Dorothee Förnzler

  6. Université Paris Descartes, AP-HP, Hôpital Européen Georges Pompidou, INSERM, Unité 765, Paris, France

    Annabelle Dupont & Pascale Gaussem

  7. Department of Medicine, University Hospital Berne, Bern, Switzerland

    Juerg H. Beer

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  1. Andrea Kopp Lugli
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Correspondence to Juerg H. Beer.

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Kopp Lugli, A., Brown, M.M., Steffel, J. et al. Platelet receptor gain-of-function single nucleotide polymorphisms in carotid and vertebral stenosis patients. J Thromb Thrombolysis 32, 215–222 (2011). https://doi.org/10.1007/s11239-011-0586-5

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