A frequent toll-like receptor (TLR)-2 polymorphism is a risk factor for coronary restenosis.
Restenosis is a major problem for patients undergoing percutaneous transluminal coronary angioplasty (PTCA). Inflammatory processes and genetic factors have been suggested to be involved in the pathogenesis of both atherosclerosis and restenosis. The recently discovered family of Toll-like receptors (TLRs) consists of molecules that initiate signaling after host-pathogen interactions. Recently it has been shown that the TLRs are involved in the development and progression of atherosclerosis by interfering with lipid metabolisms and by mediating inflammation. TLR-2 is a key innate immunity receptor for sensing both endogenous inflammatory mediators and ligands of several microbial pathogens postulated to be involved in atherosclerosis. A frequent single nucleotide polymorphism (SNP) for the TLR-2 gene, resulting in a non-functional receptor, has been described. By genotyping two independent groups of patients receiving PTCA, followed by stent implantation in one group, we found a significantly enhanced frequency of the TLR-2 Arg753Gln SNP in patients with restenosis as compared to those without restenosis (PTCA: 7.21 versus 2.45%, P = 0.014; PTCA/stent: 6.86 versus 1.53%, P = 0.013). In contrast, a common TLR-4 SNP was similarly distributed among the patient groups investigated. We furthermore compared the frequency of both SNPs in the patients with an age-matched group of individuals without atherosclerosis and found a trend towards a lower frequency of the TLR-4 SNP in the atherosclerotic group (PTCA: 5.58; PTCA/stent: 3.85 versus 7.14%). We conclude that in restenosis a functional TLR-2 is protective and potentially involved in a reaction pattern preventing restenosis. Screening for the TLR-2 Arg753Gln SNP may be of importance for stratifying a patient's risk and for preventive and therapeutic measures.
Hamann
Lutz
L
Institute for Microbiology and Hygiene, Charité University Medical Center, Humboldt University, Dorotheenstrasse 96, 10117 Berlin, Germany.
Gomma
Abuzeid
A
Schröder
Nicolas W J
NW
Stamme
Cordula
C
Glaeser
Christiane
C
Schulz
Susanne
S
Gross
Michael
M
Anker
Stefan D
SD
Fox
Kim
K
Schumann
Ralf R
RR
D023903:Coronary Restenosis / Q000209:etiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011956:Receptors, Cell Surface / Q000235:genetics*; D012307:Risk Factors; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D044465:White People / Q000235:genetics
D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors