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Genetic inflammatory factors predict restenosis after percutaneous coronary interventions

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Author: Monraats, P.S. · Pires, N.M.M. · Agema, W.R.P. · Zwinderman, A.H. · Schepers, A. · Maat, M.P.M. de · Doevendans, P.A. · Winter, R.J. de · Tio, R.A. · Waltenberger, J. · Frants, R.R. · Quax, P.H.A. · Vlijmen, B.J.M. van · Atsma, D.E. · Laarse, A. van der · Wall, E.E. van der · Jukema, J.W.
Type:article
Date:2005
Institution: TNO Kwaliteit van Leven
Source:Circulation, 16, 112, 2417-2425
Identifier: 238764
doi: doi10.1161/CIRCULATIONAHA.105.536268
Keywords: Biology · Biomedical Research · Angioplasty · Genetics · Restenosis · Risk factors · alanine · beta 2 adrenergic receptor · glycine · threonine · adult · aged · allele · Cd14 gene · colony stimulating factor 2 gene · controlled study · coronary artery disease · disease predisposition · eotaxin gene · female · gene identification · genetic polymorphism · genetic risk · haplotype · heart muscle revascularization · human · major clinical study · male · percutaneous coronary intervention · probability · prospective study · restenosis · risk assessment · risk factor · Amino Acid Substitution · Angioplasty, Transluminal, Percutaneous Coronary · Coronary Restenosis · Humans · Inflammation · Polymorphism, Single Nucleotide · Prospective Studies · Treatment Outcome

Abstract

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 β2-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. © 2005 American Heart Association, Inc. Chemicals / CAS: alanine, 56-41-7, 6898-94-8; glycine, 56-40-6, 6000-43-7, 6000-44-8; threonine, 36676-50-3, 72-19-5