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


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.
Humphries
S
S
Centre for Cardiovascular Genetics, Department of Medicine, UCLMS, The Rayne Institute, London, UK.
Bauters
C
C
Meirhaeghe
A
A
Luong
L
L
Bertrand
M
M
Amouyel
P
P
D000368:Aged; D000483:Alleles; D015906:Angioplasty, Balloon, Coronary; D019917:Blood Vessel Prosthesis Implantation; D023903:Coronary Restenosis / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D023921:Coronary Stenosis / Q000150:complications / Q000235:genetics / Q000628:therapy; D005260:Female; D005500:Follow-Up Studies; D005602:France / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors; D015607:Stents
D019278:Matrix Metalloproteinase 3