Association of MMP-9 polymorphisms with diabetic nephropathy risk

Abstract

Background: Diabetic nephropathy (DN) is a multifactorial disease with gene–environment interaction resulting in progressive renal function damage. Multiple studies have assessed the association between matrix metalloproteinase-9 (MMP-9) gene promoter polymorphism and DN susceptibility. However, the results are inconclusive. In the present study, we will conduct a meta-analysis to further examine this relationship more precisely. Methods: Electronic databases (Pubmed, Web of Science, Embase, Google Scholar, Wanfang, China Biological Medicine and China National Knowledge Infrastructure) will be used to search clinical case–control studies about MMP-9 polymorphism and DN published until 18 August 2020. The language will be restricted to Chinese and English. Two reviewers will take charge of completing the selection of study, the extraction of data as well as the assessment of study quality independently. The Newcastle-Ottawa Scale will be used to evaluate the study quality. We will evaluate the association under 5 genetic models. Fixed-effects or random-effects models will be used to calculate the effect sizes of odds ratio and 95% confidence intervals. Afterwards, subgroup analysis will be conducted in terms of the ethnicity and genotyping method. Additionally, sensitivity analysis will be performed via sequentially omitting each of the included studies one at a time. The funnel plots, Egger regression test, and Begg rank correlation test will be used to test the potential publication bias. All the statistical analyses will be performed using Review Manager 5.3 and Stata 12.0. Results: This protocol reported according to the Preferred Reporting ltems for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement. This study will provide a better understanding of the association between MMP-9 polymorphisms and DN risk. Conclusion: Publishing this protocol will minimize the potential bias related to data mining, thus contributing to generation of reliable evidence. OSF registration number: DOI 10.17605/OSF.IO/H5FS4

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

“…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]. Rather interestingly, this polymorphism exerts a protective role in a wide spectrum of diseases, such as diabetic nephropathy and anterior open bite [82,83]. In a large prospective trial (n = 1127) that included patients with CAD, the association between MMP-9 levels and the risk of fatal CV events showed a hazard ratio of 1.3, even after adjustment for confounders in terms of therapy and other clinical confounders whereas multivariate regression analysis by Ezhov et al disclosed that MMP-9 is a strong independent predictor of plaque instability in stable CAD patients [84].…”

The implication of miR-200a and miR-132 expression and their correlations with NF-κB/TNF-alpha signaling in adults with diabetic nephropathy

“…MMP-9 might be crucial for leukocyte migration and regional extracellular matrix proteolysis. Furthermore, numerous investigations have demonstrated that MMP-9 acts as a crucial inflammatory indicator, thus influencing the pathophysiology of DN ( Xie et al, 2020 ).…”

Association of matrix metalloproteinase‐2 gene variants with diabetic nephropathy risk

“…Multiple genetic variants have been identified to be linked with the pathogenesis of DN and can serve as a potential biomarker for early prevention and detection of the disease 16–28 . Matrix metalloproteinases (MMPs) are a large family of zinc and calcium dependent endopeptidases expressed in both developing and adult kidneys 29,30 .…”

“…14 Multiple genetic variants have been identified to be linked with the pathogenesis of DN and can serve as a potential biomarker for early prevention and detection of the disease. [16][17][18][19][20][21][22][23][24][25][26][27][28] Matrix metalloproteinases (MMPs) are a large family of zinc and calcium dependent endopeptidases expressed in both developing and adult kidneys. 29,30 They are critical mediators of extracellular matrix (ECM) degradation and turnover in the kidney during normal matrix remodeling.…”