The Association of MMP-2, MMP-9, and MMP-13 Gene Polymorphisms With Knee Osteoarthritis in the Greek Population

TL;DR

This study investigates how specific gene variations in the Greek population are linked to knee osteoarthritis, finding a significant association with one gene variant.

Contribution

The study identifies a novel association between the MMP-13 -77A/G polymorphism and knee osteoarthritis in the Greek population.

Findings

The MMP-13 -77A/G polymorphism is significantly associated with increased risk of knee osteoarthritis in the Greek population.

The G allele of the MMP-13 rs2252070 locus is a predictive factor for knee osteoarthritis.

MMP-2 -1575G/A and MMP-9 836A/G polymorphisms are not significantly linked to knee osteoarthritis in this population.

Abstract

Introduction

Primary knee osteoarthritis (OA) is a multifactorial degenerative joint disorder characterized by articular cartilage degradation. Matrix metalloproteinases (MMPs) have been reported to play a vital role in OA pathogenesis, significantly contributing to extracellular matrix (ECM) catabolism. The purpose of this study is to investigate the association of MMP-2 -1575G/A (rs243866), MMP-9 836A/G (rs17576), and MMP-13 -77A/G (rs2252070) gene polymorphisms with knee OA in the Greek population.

Methods

One hundred patients (24% males, mean age: 68.3 years) with primary knee OA were included in the study along with 100 controls (47% males, mean age: 65.2 years). Genotypes were identified through polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) technique. Allelic and genotypic frequencies were compared between patients and controls.

Results

The MMP-13 -77A/G polymorphism was significantly associated with knee OA in the crude analysis (P = 0.008). After binary logistic regression analysis, the dominant model of the MMP-13-77A/G (AG + GG versus AA) was found to be associated with increased risk for knee OA (odds ratio (OR) = 2.290, 95% confidence interval (95%CI) = 1.059-4.949, P= 0.035). Compared to the A allele, the G allele in the MMP-13rs2252070 locus was a predictive factor for knee OA (OR = 2.351, 95%CI = 1.134-4.874, P= 0.022). No significant associations were detected for the MMP-2 -1575G/A and MMP-9 836A/G polymorphisms (P > 0.05).

Conclusions

The present study shows that the MMP-2 -1575G/A and MMP-9 836A/G polymorphisms are not significantly associated with primary knee OA in the Greek population. The MMP-13 -77A/G was found to be a significant risk factor for knee OA in the Greek population. Additional research is needed to verify this association in larger and different populations, in different joints, to elucidate the role of this single nucleotide polymorphism (SNP) in OA pathogenesis.