The association between genetic polymorphisms of matrix metalloproteinases and knee osteoarthritis: A systematic review and meta-analysis

Int J Rheum Dis. 2024 Mar;27(3):e15123. doi: 10.1111/1756-185X.15123.

Abstract

Aim: To investigate the linkage of matrix metalloproteinase (MMP) gene polymorphisms with the pathogenesis of knee osteoarthritis (OA).

Methods: This meta-analysis study systematically retrieved relevant studies from PubMed, Embase, the Cochrane Central, Wanfang Data, CNKI, and SinoMed up to November 2020. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the association between MMP gene polymorphisms and OA.

Results: A total of nine case-control studies comprising 1719 knee OA patients and 1904 controls were included in this meta-analysis. The results revealed that MMP-1-1607 (rs1799750) 1G/2G polymorphism was not significantly associated with knee OA risk in four genetic models (OR (95% CI): allele model: 0.89 (0.57, 1.40), p = .615); dominant mode: 0.82 (0.47, 1.44), p = .486; recessive model: 0.88 (0.49, 1.57), p = .659; homozygote model: 0.79 (0.34, 1.82), p = .576. The association was significant for dominant model of MMP-3 C/T: 1.54 (1.10-2.15), p = .013, especially in Asian ethnicity (1.63 (1.11, 2.39), p = .013). Variants of MMP-13 C/T polymorphism were associated with increased risk of knee OA development based on dominant model: 1.56 (1.19, 2.06), p = .001 and homozygote model: 2.12 (1.44, 3.13), p < .001, and there were significant associations between MMP-13 C/T polymorphism and knee OA risk in Asian ethnicity under different genetic models (all p > .05).

Conclusions: Present evidence suggested that the gene polymorphisms of MMP-1-1607 1G/2G may not be associated with the risk of OA. But, the dominant model of MMP-3 and MMP-13 polymorphisms in Asian ethnicity was significantly correlated with knee OA.

Keywords: MMPs; meta‐analysis; osteoarthritis; polymorphism.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Review

MeSH terms

  • Case-Control Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Matrix Metalloproteinase 1 / genetics
  • Matrix Metalloproteinase 13 / genetics
  • Matrix Metalloproteinase 3 / genetics
  • Osteoarthritis, Knee* / diagnosis
  • Osteoarthritis, Knee* / genetics
  • Polymorphism, Single Nucleotide

Substances

  • Matrix Metalloproteinase 1
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinase 3