Abstract
Genetic factors appear to be important in the process of restenosis after percutaneous coronary intervention (PCI), as well as in inflammation, a pivotal factor in restenosis. An important mediator in the inflammatory response is interleukin (IL)-10. Our aim was to study whether genetic variants in IL-10 predispose to the risk of restenosis. The GENetic DEterminants of Restenosis (GENDER) study included 3104 patients treated with successful PCI. Target vessel revascularization (TVR) was chosen as primary end point. Genotyping of the −2849G/A, −1082G/A, −592C/A and +4259A/G polymorphisms of the IL-10 gene was performed by MassArray platform. After adjusting for clinical variables, three polymorphisms significantly increased the risk of restenosis (−2849AA: relative risk (RR), 1.7, 95% confidence interval (CI), 1.2–2.5; −1082AA: RR, 1.4, 95% CI, 1.1–1.8 and +4259GG: RR, 2.0, 95% CI, 1.4–2.8). To further exclude possible involvement of neighboring genes due to LD in the IL-10 locus, additional polymorphisms were genotyped. The results reveal that association of the IL-10 gene with restenosis is independent of flanking genes. Our findings demonstrate that IL-10 is associated with restenosis and therefore support the hypothesis that anti-inflammatory genes also may be involved in developing restenosis. Furthermore, they may provide a new targeting gene for drug-eluting stents.
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Acknowledgements
PS Monraats is supported by Grant 99.210 from the Netherlands Heart Foundation and a grant from the Interuniversity Cardiology Institute of the Netherlands (ICIN). Dr JW Jukema is an Established Clinical Investigator of the Netherlands Heart Foundation (2001 D 032). The study was supported by the Center for Medical Systems Biology (CMSB), a center of excellence approved by the Netherlands Genomics Initiative/Netherlands Organisation for Scientific Research (NWO). The contribution of the members of the clinical event committee, JJ Schipperheyn MD PhD, JW Viersma MD PhD, D Düren MD PhD and J Vainer MD, is gratefully acknowledged. We thank D Kremer and E Suchiman from the Department of Molecular Epidemiology of the Leiden University Medical Center, for their technical assistance. Furthermore, we thank MH Bax from the Department of Cardiology, A van Wengen from the Department of Infectious Diseases and M van Schie and M Kersbergen from the Department of Clinical Chemistry, all from the Leiden University Medical Center, for their technical assistance.
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Monraats, P., Kurreeman, F., Pons, D. et al. Interleukin 10: a new risk marker for the development of restenosis after percutaneous coronary intervention. Genes Immun 8, 44–50 (2007). https://doi.org/10.1038/sj.gene.6364343
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DOI: https://doi.org/10.1038/sj.gene.6364343
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