Promoter polymorphism in the CD14 gene and concentration of soluble CD14 in patients with in-stent restenosis after elective coronary stenting.
BACKGROUND
Activated monocytes/macrophages, neutrophils, endothelial cells and smooth muscle cells participate in the restenosis processes. Monocytes/macrophages and neutrophils are activated by lipopolysaccharide (LPS) via CD14. Endothelial cells and smooth muscle cells are also stimulated by soluble CD14 (sCD14)-LPS complexes.


METHODS
We tested the hypothesis that C(-260)-->T polymorphism of the CD14 gene and sCD14 might be predictors for in-stent restenosis. We analyzed 129 consecutive patients who underwent elective coronary stenting. The restenosis was defined as > or =50% diameter stenosis at follow-up angiography.


RESULTS
The prevalence of the T/T genotype and the concentration of sCD14 were significantly higher in the restenosis group than in the no-restenosis group. This CD14 polymorphism also affected the levels of sCD14, therefore, we divided the patients into four groups. The loss index was 24.8% in C/C or C/T and < or =50th percentile of sCD14, 35.9% in T/T and < or =50th percentile of sCD14, 44.2% in C/C or C/T and >50th percentile of sCD14, and 49.1% in T/T and >50th percentile of sCD14 (P=0.02). The restenosis rate was 10.0%, 26.7%, 26.2% and 50.0% in each group, respectively (P=0.003). In the multivariate analysis, T/T and >50th percentile of sCD14 was the independent predictor for in-stent restenosis.


CONCLUSIONS
This study showed that the T/T genotype with a high level of sCD14 is an independent predictor of in-stent restenosis. The activation of monocytes/macrophages, endothelial cells and smooth muscle cells mediated by CD14 and/or sCD14 may play an important role in the restenosis processes.
Department of Cardiology, Juntendo University School of Medicine, 2-1-1 Hongo Bunkyo, Tokyo 113-8421, Japan. shimakaz@med.juntendo.ac.jp
Kazunori
K
Shimada
Katsumi
K
Miyauchi
Hiroshi
H
Mokuno
Yoshiro
Y
Watanabe
Yoshitaka
Y
Iwama
Mariko
M
Shigekiyo
Megumi
M
Matsumoto
Shinya
S
Okazaki
Kosei
K
Tanimoto
Takeshi
T
Kurata
Hitoshi
H
Sato
Hiroyuki
H
Daida
D000787:Angina Pectoris / Q000628:therapy; D023903:Coronary Restenosis / Q000097:blood / Q000175:diagnosis*; D005260:Female; D005819:Genetic Markers; D006801:Humans; D007564:Japan; D018950:Lipopolysaccharide Receptors / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D015607:Stents
D005819:Genetic Markers; D018950:Lipopolysaccharide Receptors