on March 30, 2006
Published online before print March 30, 2006, doi: 10.1161/01.ATV.0000219233.31702.c9
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Submitted on August 4, 2005
Accepted on March 9, 2006
MMP-9 Microsatellite Polymorphism and Susceptibility to Carotid Arteries Atherosclerosis
Nicola Fiotti *;
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.
* To whom correspondence should be addressed. 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.
Key words: atherosclerosis • carotid arteries • MMP-9 • polymorphism • stroke