Copyright © 2002 by the European Society of Cardiology.
The 5A6A polymorphism in the promoter of the stromelysin-1 (MMP3) gene as a risk factor for restenosis
a Centre for Cardiovascular Genetics, Department of Medicine, UCLMS, The Rayne Institute, London, U.K.
b INSERMU508, Institut Pasteur de Lille, Lille, France
c University and CHRU de Lille, Lille, France
revised July 11, 2001; accepted July 18, 2001
Abstract
Aims Intracoronary ultrasound studies in humans show that chronic remodelling rather than neointimal hyperplasia is the mechanism of restenosis. Stent implantation limits this remodelling process and significantly reduces restenosis. MMP3 (Stromelysin-1), a member of the matrix metalloproteinase family may play a role in this remodelling. We used a functional polymorphism (with alleles designated 5A or 6A) in the promoter of the MMP3 gene to examine the possible role of MMP3 in restenosis.
Methods and Results Genotypes were determined in a series of consecutive patients who underwent conventional balloon coronary angioplasty without stenting (n=287) or who also had successful implantation of a Palmaz–Schatz stent (stent) (n=198). For all patients restenosis was estimated at 6 months using quantitative computer-assisted angiography. The minimal luminal diameters before and after the procedures did not differ significantly between genotypes. At follow-up in the patients without stent, those with the 6A6A genotype had an increased degree of restenosis after coronary angioplasty compared to those with one or more 5A alleles, with a greater diameter stenosis (52±21% vs 45±19%, P=0·012), and a greater late loss (0·58±0·59mm vs 0·38±0·59mm, P=0·038). By contrast, in the stented patients MMP3 genotype was not associated with any angiographically determined measure of vessel dimensions.
Conclusions These data imply the involvement of MMP3 in chronic remodelling after conventional balloon angioplasty, and suggest that the 6A6A MMP3 genotype is a genetic susceptibility factor for restenosis after angioplasty without stenting.
Key Words: Stromelysin (MMP-3), restenosis, stent, genetic polymorphism, vascular remodelling
f1 Correspondence: Professor Steve Humphries, Centre for Cardiovascular Genetics, Department of Medicine, UCLMS, The Rayne Institute, 5 University Street, London WC1E 6JJ, U.K.
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