Association of tumor necrosis factor-α (G-308A) genetic variant with matrix metalloproteinase-9 activity and joint destruction in early rheumatoid arthritis.

Abstract

Matrix metalloproteinases (MMPs) are the key enzymes responsible for the joint destruction. Their activity is regulated by the level of proinflammatory cytokines. The aim of this study was to examine the impact of TNF-α G-308A polymorphism on MMP-9 levels in blood plasma (BP) and synovial fluid (SF) of patients with rheumatoid arthritis (RA) and their role in progression of joint destruction. One hundred thirty-four subjects were enrolled in this study. TNF-α G-308A polymorphism was determined using PCR-RFLP method. ELISA assay was used for the detection of MMP-9 activity in BP and SF. Joint damage was estimated by hands and feet radiography. Larsen score and annual changes in LS were used for quantitative evaluation of joint destruction and radiographic progression of disease. MMP-9 activity in BP and SF was significantly higher in RA compared to controls, as well as in SF of patients with erosive compared to nonerosive RA. Faster radiographic progression and increased MMP-9 activity in BP and SF were detected in the group A (GA or AA genotype carriers) compared to the group G (GG genotype carriers). However, statistical significance was revealed only for MMP-9 activity in SF (p<0.05). MMP-9 activity in BP and SF is significantly higher in RA patients compared to patients with osteoarthritis. The presence of TNF-α-308A allele is associated with increased MMP-9 activity in SF of patients with early RA and may be a predictor of rapid radiographic progression of disease.