The 5A6A polymorphism in the promoter of the stromelysin-1 (MMP3) gene as a risk factor for restenosis

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+/-0.59 mm vs 0.38+/-0.59 mm, 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.