Genetic inflammatory factors predict restenosis after percutaneous coronary interventions.
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.


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 beta2-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.
Monraats
Pascalle S
PS
Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
Pires
Nuno M M
NM
Agema
Willem R P
WR
Zwinderman
Aeilko H
AH
Schepers
Abbey
A
de Maat
Moniek P M
MP
Doevendans
Pieter A
PA
de Winter
Robbert J
RJ
Tio
René A
RA
Waltenberger
Johannes
J
Frants
Rune R
RR
Quax
Paul H A
PH
van Vlijmen
Bart J M
BJ
Atsma
Douwe E
DE
van der Laarse
Arnoud
A
van der Wall
Ernst E
EE
Jukema
J Wouter
JW
D019943:Amino Acid Substitution; D015906:Angioplasty, Balloon, Coronary; D023903:Coronary Restenosis / Q000235:genetics*; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D016896:Treatment Outcome