The E-selectin SER128ARG gene polymorphism and restenosis after successful coronary angioplasty.
OBJECTIVE
Coronary angioplasty remains plagued by the problem of restenosis. Genetic polymorphisms may contribute to the development of restenosis by mediating exaggerated inflammatory responses of the endothelium to angioplasty-induced injury.


BACKGROUND
The serine (Ser)-128-arginine (Arg) gene polymorphism of E-selectin has been implicated in the pathogenesis of coronary artery disease (CAD). We sought to explore whether allelic variants relate to post-angioplasty restenosis.


METHODS
The 128Arg allele was analyzed by PCR in 101 (derivation study, age 54+/-1 years, all mean+/-S.E.M.) and 92 (validation study, age 62+/-1 years) patients with CAD who underwent successful angioplasty.


RESULTS
Restenosis, defined as >50% luminal diameter reduction at the target lesion at follow-up angiography, was found in 54/101 (53%) and 43/92 (47%) patients during follow-up. The 128Arg allele frequency in the derivation study was 10.39% and was 11.96% in the validation study. The 128Arg allele was more prevalent in the restenosis groups (14.81% and 17.44%, respectively) than in the restenosis-free groups (5.32% and 7.14%, respectively, p=0.027 and p=0.031). In multivariate logistic regression, the 128Arg allele emerged as a predictor of restenosis in both studies (p<0.05). There were no differences in the level of soluble E-selectin according to genotype, gender, age (p>0.20), and between patients with restenosis and those without (43.8+/-3.2 vs. 47.4+/-3.1 ng/ml, p>0.20).


CONCLUSIONS
The 128Arg allele of E-selectin may be related to increased endothelial responses to injury, thereby potentially serving as a risk factor for post-angioplasty restenosis in patients with CAD.The development of restenosis remains a problem in patients with CAD. The Ser128Arg polymorphism of E-selectin was analyzed in 101 (derivation) and 92 (validation) CAD patients. Patients with restenosis (54/101 and 43/92) had a higher frequency of the 128Arg allele (14.81 and 17.44%) than those without (5.32%, p=0.027 and 7.14%, p=0.031). In logistic regression, the 128Arg allele emerged as a predictor of restenosis in both studies (p<0.05). The E-selectin 128Arg allele may serve as a risk factor for the development of restenosis.
Rauchhaus
Mathias
M
Klinik und Poliklinik für Innere Medizin III, Martin-Luther-Universität Halle-Wittenberg, Ernst-Grube-Strasse 40, D-06097 Halle/Saale, Germany. mathias.rauchhaus@medizin.uni-halle.de
Gross
Michael
M
Schulz
Susanne
S
Francis
Darrel P
DP
Greiser
Petra
P
Norwig
Antje
A
Weidhase
Lorenz
L
Coats
Andrew J S
AJ
Dietz
Rainer
R
Anker
Stefan D
SD
Gläser
Christiane
C
D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D001120:Arginine / Q000235:genetics; D017023:Coronary Angiography; D003327:Coronary Disease / Q000235:genetics* / Q000628:therapy; D023903:Coronary Restenosis / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011237:Predictive Value of Tests; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*; D012694:Serine / Q000235:genetics; D012795:Sialoglycoproteins; D016896:Treatment Outcome
D008562:Membrane Glycoproteins; D017468:Receptors, Fibroblast Growth Factor; D012795:Sialoglycoproteins; C086711:cysteine-rich fibroblast growth factor receptor; D012694:Serine; D001120:Arginine