Abstract
Matrix metalloproteinases (MMPs) play an important role in the pathogenesis of atherosclerosis, the pathology underlying the majority of coronary artery disease (CAD). In this study we tested the hypothesis that polymorphic variation in the MMP genes influences the risk of developing atherosclerosis. We analyzed functional polymorphisms in the promoter of the MMP-1, MMP-3, MMP-9 and MMP-12 genes in 183 Brazilian Caucasian individuals submitted to coronary angiography, of which 67 (37%) had normal coronary arteries (control group) and 116 (63%) had CAD (CAD patient group). The -1607 1G/2G MMP-1, -1171 5A/6A MMP-3, -1562 C/T MMP-9, -82 A/G MMP-12 polymorphisms were analyzed by PCR followed by restriction digestion. No significant differences were observed in allele frequencies between the CAD patients and controls. Haplotype analysis showed no differences between the CAD patients and controls. There was a significant difference in the severity of CAD, as assessed by the number of diseased vessels, in MMP-1 1G/1G homozygous individuals and in those homozygous for the 6A allele of the MMP-3 polymorphism. However, multivariate analysis showed that diabetes mellitus was the only variable independently associated with CAD severity. Our findings indicated that MMP polymorphisms have no significant impact on the risk and severity of CAD.
Highlights
Atherosclerosis, the underlying pathology of coronary artery disease (CAD), is a common, multifactorial disorder with both genetic and environmental components
The aim of the study reported in this paper was to ascertain if polymorphisms in the promoter of Matrix metalloproteinases (MMPs)-1, MMP-3, MMP-9 and MMP-12 genes are associated with the risk of developing CAD in a Brazilian population of European ancestry
No significant differences were observed in genotype frequencies between the 116 CAD patients and 67 control individuals for any of the polymorphisms analyzed
Summary
Atherosclerosis, the underlying pathology of coronary artery disease (CAD), is a common, multifactorial disorder with both genetic and environmental components. Previous studies have found that MMP-1 (interstitial collagenase), MMP-3 (stromelysin-1), MMP-9 (92-kD gelatinase or gelatinase B) and MMP-12 (macrophage metalloelastase) are expressed in atheroma at high levels compared with normal vessel walls (Jones et al, 2003; Newby, 2005). These MMPs have the capacity to degrade virtually all components of the extracellular matrix in the arterial wall (collagens, elastin, proteoglycans, laminin, fibronectin, etc.). The aim of the study reported in this paper was to ascertain if polymorphisms in the promoter of MMP-1, MMP-3, MMP-9 and MMP-12 genes are associated with the risk of developing CAD in a Brazilian population of European ancestry
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