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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:1330.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

MMP-9 Microsatellite Polymorphism and Susceptibility to Carotid Arteries Atherosclerosis

Nicola Fiotti; Nicola Altamura; Maurizio Fisicaro; Nicola Carraro; Laura Uxa; Gabriele Grassi; Lucio Torelli; Raffaella Gobbato; Gianfranco Guarnieri; B. Timothy Baxter; Carlo Giansante

From U.C.O. di Clinica Medica Generale e Terapia Medica (N.F., N.A., G.G., R.G., G. Guarnieri, C.G.), Dipartimento di Scienze Cliniche Morfologiche e Tecnologiche, University of Trieste, Trieste, Italy; Cardiovascular Center (M.F.), A.S.S. no 1 Triestina, Trieste, Italy; U.C.O. di Neurologia (N.C.), Dipartimento di Medicina Clinica e Neurologia. University of Trieste, Trieste, Italy; Blood Transfusion Center (L.U.), A.S.S. no 1 Triestina, Trieste, Italy; Department of Mathematics and Informatics (L.T.), University of Trieste, Trieste, Italy; Department of Surgery (T.B.), University of Nebraska Medical Center, Omaha, Ne.

Correspondence to Nicola Fiotti, MD, U.C.O. di Clinica Medica Generale e Terapia Medica, Strada di Fiume, 447, 34149 Trieste, Italy. E-mail fiotti{at}units.it

Objective— The aims of this study were to compare a microsatellite polymorphism (PM) of matrix metalloproteinase (MMP)-9 in patients with carotid atherosclerosis and control population, and to assess the relationship between this PM and plaque structure.

Methods and Results— One hundred fifty patients referring to vascular diagnostic centers for suspected carotid atherosclerosis (at ultrasound examination: 110 positive, 40 negative) and controls (n=110) have been genotyped for MMP-9 PM. After controlling for risk factors, allelic and genotype frequencies were significantly different among the groups, with significant prevalence of long microsatellites in patients with carotid atherosclerosis. Long microsatellites (settled as 22 to 27 repeats) were associated with carotid atherosclerosis (odds ratio [OR], 5.2; 95% confidence interval [CI], 2.9 to 9.2), compared with controls; an independent case control study on patients with coronary atherosclerosis confirmed such result. Binary logistic regression showed that hypertension, long microsatellites in MMP-9 PM and smoking habits were variables accounting for the difference between ultrasound-positive patients and controls. Long microsatellites were also associated to plaques with thin fibrous cap and echolucent core (OR, 13.1; 95% CI, 1.6 to 100). These alleles were slightly more represented in female patients (² test=0.019; OR, 2.7; 95% CI, 1.2 to 6) but not associated with other risk factors. Plasma MMP-9 levels were related neither to MMP-9 PM nor to plaque type, and were related to gender and extension of atherosclerosis in carotid arteries.

Conclusions— The number of repeats (22 CA) in the microsatellite of MMP-9 promoter, but not MMP-9 plasma levels, is associated to carotid atherosclerosis and particularly to plaques with a thin fibrous cap.

Higher prevalence of long microsatellites (22 CA repeats) in MMP-9 promoter was found in patients with ultrasound evidence of carotid atherosclerosis and, among them, in carriers of plaques with a thin fibrous cap and echolucent core. This PM was independent of known risk factors for atherosclerosis and did not influence MMP-9 plasma levels.

Key Words: atherosclerosis • carotid arteries • MMP-9 • polymorphism • stroke