1. ¹Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
2. ²Interuniversity Cardiology Institute of The Netherlands (ICIN), Utrecht, The Netherlands
3. ³Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
4. ⁴Department of Medical Statistics, Academic Medical Center, Amsterdam, The Netherlands
5. ⁵Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands
6. ⁶Department of Cardiology, University Medical Center, Utrecht, The Netherlands
7. ⁷Department of Cardiology, Academic Medical Center, Amsterdam, The Netherlands
8. ⁸Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands
9. ⁹Department of Cardiology, Academic Hospital Maastricht, Maastricht, The Netherlands
10. ¹⁰Gaubius Laboratory, TNO Quality of Life, Leiden, The Netherlands
11. ¹¹Department of Vascular Surgery, Leiden University Medical Center, Leiden, The Netherlands
12. ¹²Department of Human Genetics, Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands

Correspondence: Professor Dr JW Jukema, Department of Cardiology C5-P, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands. E-mail: j.w.jukema@lumc.nl

Received 5 July 2006; Revised 30 August 2006; Accepted 31 August 2006; Published online 23 November 2006.

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.