Title
Genetic inflammatory factors predict restenosis after percutaneous coronary interventions
Author
Monraats, P.S.
Pires, N.M.M.
Agema, W.R.P.
Zwinderman, A.H.
Schepers, A.
de Maat, M.P.M.
Doevendans, P.A.
de Winter, R.J.
Tio, R.A.
Waltenberger, J.
Frants, R.R.
Quax, P.H.A.
van Vlijmen, B.J.M.
Atsma, D.E.
van der Laarse, A.
van der Wall, E.E.
Jukema, J.W.
TNO Kwaliteit van Leven
Publication year
2005
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
Subject
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
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http://resolver.tudelft.nl/uuid:5bf0a25b-ccf0-435b-a533-80828627cd30
DOI
https://doi.org/10.1161/circulationaha.105.536268
TNO identifier
238764
ISSN
0009-7322
Source
Circulation, 112 (16), 2417-2425
Document type
article