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A frequent toll-like receptor (TLR)-2 polymorphism is a risk factor for coronary restenosis

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Abstract

Restenosis is a major problem for patients undergoing percutaneous transluminal coronary angioplasty (PTCA). Inflammatory processes and genetic factors have been suggested to be involved in the pathogenesis of both atherosclerosis and restenosis. The recently discovered family of Toll-like receptors (TLRs) consists of molecules that initiate signaling after host-pathogen interactions. Recently it has been shown that the TLRs are involved in the development and progression of atherosclerosis by interfering with lipid metabolisms and by mediating inflammation. TLR-2 is a key innate immunity receptor for sensing both endogenous inflammatory mediators and ligands of several microbial pathogens postulated to be involved in atherosclerosis. A frequent single nucleotide polymorphism (SNP) for the TLR-2 gene, resulting in a non-functional receptor, has been described. By genotyping two independent groups of patients receiving PTCA, followed by stent implantation in one group, we found a significantly enhanced frequency of the TLR-2 Arg753Gln SNP in patients with restenosis as compared to those without restenosis (PTCA: 7.21 versus 2.45%, P=0.014; PTCA/stent: 6.86 versus 1.53%, P=0.013). In contrast, a common TLR-4 SNP was similarly distributed among the patient groups investigated. We furthermore compared the frequency of both SNPs in the patients with an age-matched group of individuals without atherosclerosis and found a trend towards a lower frequency of the TLR-4 SNP in the atherosclerotic group (PTCA: 5.58; PTCA/stent: 3.85 versus 7.14%). We conclude that in restenosis a functional TLR-2 is protective and potentially involved in a reaction pattern preventing restenosis. Screening for the TLR-2 Arg753Gln SNP may be of importance for stratifying a patient’s risk and for preventive and therapeutic measures.

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Acknowledgements

This work was supported by the DFG [Innate Immunity, Project Schr 726, 1-2 (to N.W.J.S. and R.R.S.), SFB 633-03, Project A7 (to R.R.S.)], and by the British Heart Foundation.

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Authors and Affiliations

  1. Institute for Microbiology and Hygiene, Charité University Medical Center, Humboldt University, Dorotheenstrasse 96, 10117, Berlin, Germany

    Lutz Hamann, Nicolas W. J. Schröder & Ralf R. Schumann

  2. Cardiology Department, National Heart and Lung Institute and Royal Brompton Hospital, London, UK

    Abuzeid Gomma, Stefan D. Anker & Kim Fox

  3. Department of Anesthesiology, University of Lübeck and Research Center Borstel, Lübeck, Germany

    Cordula Stamme

  4. Institute of Human Genetics and Medical Biology, University of Halle, Halle, Germany

    Christiane Glaeser & Susanne Schulz

  5. Department of Cardiology, Charité University Medical Center, Berlin, Germany

    Michael Gross & Stefan D. Anker

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  1. Lutz Hamann
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Correspondence to Ralf R. Schumann.

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L. Hamann and A. Gomma contributed equally to this work

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Hamann, L., Gomma, A., Schröder, N.W.J. et al. A frequent toll-like receptor (TLR)-2 polymorphism is a risk factor for coronary restenosis. J Mol Med 83, 478–485 (2005). https://doi.org/10.1007/s00109-005-0643-7

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  • DOI: https://doi.org/10.1007/s00109-005-0643-7

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