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(Circulation. 2005;112:2417-2425.)
© 2005 American Heart Association, Inc.

Genetics

Genetic Inflammatory Factors Predict Restenosis After Percutaneous Coronary Interventions

Pascalle S. Monraats, MSc; Nuno M.M. Pires, MSc; Willem R.P. Agema, MD, PhD; Aeilko H. Zwinderman, PhD; Abbey Schepers, MD; Moniek P.M. de Maat, PhD; Pieter A. Doevendans, MD, PhD; Robbert J. de Winter, MD, PhD; René A. Tio, MD, PhD; Johannes Waltenberger, MD, PhD; Rune R. Frants, PhD; Paul H.A. Quax, PhD; Bart J.M. van Vlijmen, PhD; Douwe E. Atsma, MD, PhD; Arnoud van der Laarse, PhD; Ernst E. van der Wall, MD, PhD; J. Wouter Jukema, MD, PhD

From the Department of Cardiology (P.S.M., N.M.M.P., W.R.P.A., B.J.M.v.V., D.E.A., A.v.d.L., E.E.V.D.W., J.W.J.), the Department of Surgery (A.S., P.H.A.Q.), and the Department of Human Genetics, Center for Human and Clinical Genetics (R.R.F.), Leiden University Medical Center, Leiden; Interuniversity Cardiology Institute of the Netherlands (ICIN) (P.S.M., W.R.P.A., P.A.D., J.W.J.), Utrecht; Gaubius Laboratory, TNO PG (N.M.M.P., A.S., P.H.A.Q., B.J.M.v.V.), Leiden; the Department of Medical Statistics (A.H.Z.) and the Department of Cardiology (R.J.d.W.), Academic Medical Center, Amsterdam; the Department of Hematology, Erasmus University Medical Center (M.P.M.d.M.), Rotterdam; the Department of Cardiology, HLCU, University Medical Center Utrecht (P.A.D.); the Department of Cardiology, University Medical Center Groningen (R.A.T.); and the Department of Cardiology, Academic Hospital Maastricht (J.W.), Maastricht, the Netherlands.

Correspondence to Dr J.W. Jukema, Leiden University Medical Center, Department of Cardiology, C5-P, Albinusdreef 2, PO Box 9600, 2300 RC Leiden, The Netherlands. E-mail J.W.Jukema{at}lumc.nl

Received July 8, 2004; de novo received January 14, 2005; revision received June 24, 2005; accepted July 1, 2005.

Background— Restenosis is a negative effect of percutaneous coronary intervention (PCI). No clinical factors are available that allow good risk stratification. However, evidence exists that genetic factors are important in the restenotic process as well as in the process of inflammation, a pivotal factor in restenosis. Association studies have identified genes that may predispose to restenosis, but confirmation by large prospective studies is lacking. Our aim was to identify polymorphisms and haplotypes in genes involved in inflammatory pathways that predispose to restenosis.

Methods and Results— The GENetic DEterminants of Restenosis (GENDER) project is a multicenter prospective study, including 3104 consecutive patients after successful PCI. Forty-eight polymorphisms in 34 genes in pathways possibly involved in the inflammatory process were analyzed. The 16Gly variant of the ß₂-adrenergic receptor gave an increased risk of target vessel revascularization (TVR). The rare alleles of the CD14 gene (–260T/T), colony-stimulating factor 2 gene (117Thr/Thr), and eotaxin gene (–1328A/A) were associated with decreased risk of TVR. However, through the use of multiple testing corrections with permutation analysis, the probability of finding 4 significant markers by chance was 12%.

Conclusions— Polymorphisms in 4 genes considered involved in the inflammatory reaction showed an association with TVR after PCI. Our results may contribute to the unraveling of the restenotic process. Given the explorative nature of this analysis, our results need to be replicated in other studies.

Key Words: genetics • restenosis • risk factors • inflammation • angioplasty

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