Association between matrix metalloproteinase-3 gene polymorphisms and tendon-ligament injuries: evidence from a meta-analysis

Abstract

Background Tendon-ligament injuries (TLIs), including Achilles tendinopathy, cruciate ligament injury, tennis elbow, rotator cuff injury, patellar tendinopathy, and tibial tendinopathy, are common musculoskeletal soft injuries during physical activity. Matrix metalloproteinase-3 (MMP-3) gene polymorphisms have been implicated in the etiology of TLIs in several genetic association studies with inconsistent results. The purpose of this study was to collect and synthesize the current evidences on the association of MMP-3 polymorphisms and TLIs. Methods The search was conducted using PubMed, Web of Science, EMBASE, Cochrane Library, CNKI and Wanfang databases, prior to July, 2021. Newcastle Ottawa Scale was used to appraise the study quality. Strengths of association were represented by odds ratios (ORs) and 95% confidence intervals (95% CIs). Results Thirteen studies with 2871 cases and 4497 controls met the eligibility criteria, and each study was in high quality. The overall analyzes suggested rs3025058 was associated with an increased TLIs risk (5A vs. 6A, OR = 1.20, 95% CI 1.03–1.40, P = 0.020). However, the association was not found for rs679620, rs591058, and rs650108 polymorphisms. Subgroup analysis by injury type suggested that rs679620 polymorphism was associated with a reduced risk to Achilles tendon rupture (AA + AG vs. GG, OR = 0.46, 95% CI 0.25–0.87, P = 0.020), and rs3025058 was associated with an elevated risk to anterior cruciate ligament injury (5A5A + 5A6A vs. 6A6A, OR = 1.46, 95% CI 1.03–2.06, P = 0.030). When stratified by ethnicity, the findings indicated that rs3025058 polymorphism was associated with an increased TLIs risk among Caucasians (5A6A vs. 6A6A, OR = 1.55, 95% CI 1.09–2.42, P = 0.020) and Brazilians (5A5A vs. 5A6A + 6A6A, OR = 2.80, 95% CI 1.44–5.45, P = 0.002). Conclusion Findings of this study suggest that rs679620 polymorphism is associated with a reduced Achilles tendon rupture risk, and rs3025058 polymorphism contributes to an increased TLIs risk in Caucasians and Brazilians. However, rs591058 and rs650108 polymorphisms do not show any association with TLIs.

What Role Does PDGFA Gene Polymorphisms Play in Treating Tennis Elbow with PRP? A Prospective Cohort Study

“…Due to the applied research model, their results are characterized by high variability resulting from different criteria for selecting the study and control groups, as well as ethnic differences. In the light of current knowledge, well-established factors of susceptibility to tendinopathy are the polymorphic variants of collagen, type I, alpha-1 ( COL1A1 ) [ 33 ], collagen, type V, alpha-1 ( COL5A1 ) [ 34 ] and matrix metalloproteinase 3 ( MMP3 ) [ 35 ] genes. However, little is known about their effect on the prognosis of tennis elbow therapy, as such studies have not been conducted so far.…”

Hypoxia-Inducible Factor and Oxidative Stress in Tendon Degeneration: A Molecular Perspective

“…In addition to MMP-2 and MMP-9, MMP-3 has been found to be dysregulated during tendinopathies, which is inconsistent with its expected role in matrix remodeling. A study also suggested that the expression of MMP-3 is suppressed during tendinopathy, and MMP-3 polymorphism may contribute to chronic tendon disorders [67]. As MMP-3 also plays a crucial role in matrix remodeling, the downregulation or complete inhibition of MMP-3 by TIMP-1 would imply the failure of proper matrix remodeling [68].…”

Optimizing repair of tendon ruptures and chronic tendinopathies: Integrating the use of biomarkers with biological interventions to improve patient outcomes and clinical trial design

“…Additionally, just as there appear to be genetic markers for good outcomes after rupture of tendons such as the Achilles and rotator cuff tendons, genetic risk for tearing/rupturing such tendons has also been reported (116)(117)(118)(119)(120)(121)(122)(123). Thus, the biomarkers that are proteins result from gene expression (to variable levels dependent on regulation at the DNA level) while genetic risk for injury is in the genome (DNA and potentially epigenetically modified DNA) but how such genomic risk is translated to risk at the tissue level is still largely unknown.…”

“…Thus, the biomarkers that are proteins result from gene expression (to variable levels dependent on regulation at the DNA level) while genetic risk for injury is in the genome (DNA and potentially epigenetically modified DNA) but how such genomic risk is translated to risk at the tissue level is still largely unknown. While some of these studies are based on risk in twins (123), others have indicated that variations in specific molecules such as MMP-3 (122), iNOS (119), or extracellular matrix genes such as COL1A1 (117) pose risk. Ultimately, there will be a need to integrate the risk factors for injury with those for good and poor healing outcomes to obtain a more complete picture of the landscape in individual patients.…”