Toll-like receptor 4 gene polymorphisms show no association with the risk of clinical or angiographic restenosis after percutaneous coronary intervention.
OBJECTIVE
Restenosis after percutaneous coronary intervention (PCI) remains an issue even in the drug-eluting stent era. Genetic polymorphisms may provide insight in the pathogenesis of restenosis and may help in the stratification of patients at risk for restenosis. The aim of this study was to examine whether polymorphisms at the toll-like receptor 4 (TLR4) locus, that are associated with impaired innate immune system and with an increased risk of cardiovascular events, were associated with clinical and/or angiographic restenosis after PCI.


METHODS
The GENetic Determinants of Restenosis (GENDER) project was a prospective, multicenter study that enrolled 3146 consecutive patients after successful PCI. Frequencies of the TLR4 896A/G (Asp299Gly; rs4986790) and 1196C/T (Thr399Ile; rs4986791) polymorphisms and haplotypes were assessed. Patients were followed up for 1 year and in a subgroup of 406 patients angiographic follow-up was obtained.


RESULTS
We included a total of 2682 patients that underwent successful PCI. There was no association between genotypes and the risk of target vessel revascularization at 1-year or late luminal loss at 6-months angiographic follow-up (P=0.53 and 0.44, respectively). Absence of association with target lesion revascularization and late luminal loss was replicated in the GEnetic risk factors for In-Stent Hyperplasia study Amsterdam (GEISHA) cohort study of 674 patients and in a subgroup of 550 patients with angiographic follow-up available (P=0.26, and 0.86, respectively). Moreover, in both the studies, no significant differences between haplotypes A/C and G/T were observed for target vessel revascularization at late luminal loss.


CONCLUSIONS
Although inflammation has been implicated in the pathophysiology of restenosis, the 896A/G and 1196C/T polymorphisms or haplotypes based on these polymorphisms at the TLR4 locus are not associated with an increased risk of target vessel revascularization or angiographic restenosis after PCI. These polymorphisms are not useful for pre-PCI identification of patients at risk for restenosis.
Beijk
Marcel A M
MA
Department of Cardiology, Academic Medical Center, University of Amsterdam, The Netherlands.
Boekholdt
S Matthijs
SM
Rittersma
Saskia Z H
SZ
Pons
Douwe
D
Zwinderman
Aeilko H
AH
Doevendans
Pieter A F
PA
Tio
Rene A
RA
Tijssen
Jan G P
JG
Jukema
J Wouter
JW
de Winter
Robbert J
RJ
D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D017023:Coronary Angiography; D023903:Coronary Restenosis / Q000209:etiology* / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D016896:Treatment Outcome
C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4