The association between Matrix Metallo-proteinases-9 (MMP-9) gene family polymorphisms and risk of Coronary Artery Disease (CAD): a systematic review and meta-analysis

Abstract

Background: We performed a systematic review and meta-analysis of the Matrix metalloproteinases (MMP)-9 (C1562T), MMP-9 (R279Q), MMP-9 (P574R) and MMP-9 (R668Q) polymorphisms and risk of Coronary Artery Disease (CAD). Methods: After a systematic literature search, pooled odds ratio (OR) and their corresponding 95% confidence interval (CI) were used to evaluate the strength of the association. Results: We identified 40 studies with 11,792 cases and 8280 controls for C1562T, 7 case-control studies with 5525 cases and 2497 controls for R279Q, 2 studies with 1272 cases and 785 controls for P574R, and 2 studies with 1272 cases and 785 controls for R668Q. MMP-9 (C1562T) polymorphism was associated with increased risk of CAD under dominant model (OR = 1.41, P < 0.001), recessive model (OR = 1.59, P < 0.001), allelic model (OR = 1.38, P < 0.001), TT vs. CC model (OR = 1.70, P < 0.001), and CT vs. CC model (OR = 1.35, P < 0.001). Moreover, the subgroup analysis based on the continent of the study populations in this SNP indicated strong significant association in Asians but not in Europeans. Subgroup analysis was not performed in Africa, America and Oceania, due to lack of sufficient data. Conclusions: Our meta-analysis revealed that MMP-9 (C1562T) SNP conferred a susceptibility risk for CAD in the overall analysis and Asian population. The overall analysis and subgroup analysis of the other three SNPs reject the association between MMP-9 polymorphisms and the risk of CAD. Although the results should interpret with caution because of small sample size of included studies in these three SNPs.

Ligand-based pharmacophore modeling and molecular dynamic simulation approaches to identify putative MMP-9 inhibitors

“…The DDHRR_1 model consists of two hydrophobic, two ring features, and a hydrogen bond donor. Aer the alignment of hypothesis DDHRR_1 over actives (10) and inactives (7) revealed that angles and distances are significant attributes for inhibitory activity of MMP-9. Besides, a higher degree of condence in the hypothesis model DDHRR_1 was exhibited by the higher value of QSAR model stability 0.709 on a maximum scale of 1 with an SD of 0.3473, root-mean-square-error (RMSE) of 0.48, and Pearson correlation coefficient (r) of 0.9454.…”

“…3,4 However, this balance is lost in numerous pathological conditions, causing chronic inammation. 5 This chronic condition is responsible for abnormal tissue degradation, causing cancers, 6,7 atherosclerosis, 8 osteoarthritis, 9 cardiovascular, 10,11 lung, 12,13 neurological, 14,15 metabolic-related disorders, and delayed wound healing in diabetes. 16 Thus, nding novel inhibitors that block the elevated levels of MMP-9 could be an attractive approach in combating the pathogenesis of several diseases.…”

Circulating Biomarkers Reflecting Destabilization Mechanisms of Coronary Artery Plaques: Are We Looking for the Impossible?

“…The most consistent evidence with respect to association of MMP-9 polymorphisms and CAD is that regarding the C1562T polymorphism. In a recent meta-analysis, Hassanzadeh-Makoui et al demonstrated that MMP-9 (C1562T) polymorphism was associated with increased risk of CAD susceptibility in the overall analysis, but markedly in the Asian population [80]. The pathophysiological background of this association is the fact that this variant of MMP-9 decreases binding potential of the proteins involved in the inhibition of transcription to the DNA sequence, thus playing a role in orchestrating the transcription activity of MMP-9 [81].…”

Association between MMP-2 gene polymorphism and cataract susceptibility

“…Matrix metalloproteinases (MMPs) refer to a class of proteolytic enzymes that can hydrolyze extracellular matrix. [ 11 , 12 ] Based on some researches, the invasion and metastasis of cells are related to the degradation of extracellular matrix. [ 13 , 14 ] As an important member of the MMPs family, matrix metalloproteinase-2 (MMP-2) is a proteolytic enzyme based on type IV collagen and laminin, which can specifically degrade the matrix components of normal lens capsule.…”