MMP-9 microsatellite polymorphism and susceptibility to carotid arteries atherosclerosis
Nicola Fiotti1, Nicola Altamura, Maurizio Fisicaro
1U.C.O. di Clinica Medica Generale e Terapia Medica, Dipartimento di Scienze Cliniche Morfologiche e Tecnologiche, University of Trieste, Trieste, Italy. fiotti@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 (chi2 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 (> or =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.
Insights
A specific gene variant in matrix metalloproteinase (MMP)-9, characterized by long microsatellites, is linked to carotid atherosclerosis. This genetic marker is also associated with vulnerable plaque structures, indicating potential diagnostic value.
Area of Science:
- Genetics
- Cardiovascular Medicine
- Molecular Biology
Background:
- Carotid atherosclerosis is a significant risk factor for stroke.
- Matrix metalloproteinase-9 (MMP-9) plays a role in plaque instability.
- Microsatellite polymorphisms (PM) in gene promoters can influence gene expression and disease susceptibility.
Purpose of the Study:
- To investigate the association between an MMP-9 microsatellite polymorphism and carotid atherosclerosis.
- To determine if this polymorphism correlates with specific plaque characteristics.
- To compare MMP-9 PM frequencies in patients with carotid atherosclerosis and controls.
Main Methods:
- Genotyping of 150 patients with suspected carotid atherosclerosis and 110 controls for MMP-9 PM.
- Analysis of allelic and genotype frequencies, controlling for risk factors.
- Logistic regression to identify independent risk factors for carotid atherosclerosis and plaque type.
Main Results:
- Long microsatellites (22-27 repeats) in MMP-9 PM were significantly more prevalent in patients with carotid atherosclerosis (OR, 5.2).
- This association was confirmed in an independent cohort with coronary atherosclerosis.
- Long microsatellites were independently associated with hypertension, smoking, and vulnerable plaques (thin fibrous cap, echolucent core; OR, 13.1).
- Allele frequency was slightly higher in females but not linked to other risk factors.
Conclusions:
- The number of repeats in the MMP-9 promoter microsatellite is associated with carotid atherosclerosis.
- This genetic variant is particularly linked to the development of plaques with thin fibrous caps.
- MMP-9 plasma levels were not associated with the microsatellite polymorphism or plaque type.
