MMP-3 gene polymorphisms are associated with increased risk of osteoarthritis in Chinese men

Abstract

Osteoarthritis (OA) is the most common late-onset degenerative joint disease., It is characterized by progressive degradation of articular cartilage. We investigated the association between OA occurrence and single nucleotide polymorphisms (SNPs) in the matrix metalloproteinase-3 (MMP-3) gene involved in the breakdown of extra-cellular matrix proteins. The study included 100 male OA patients and 197 healthy men from the north area of China. Eight MMP-3 SNPs were genotyped. Odds ratios (ORs) with 95% confidence intervals (95%CIs) and multivariate logistic regression analysis were used to assess the association. Multivariate logistic regression analysis was used to identify SNPs that correlated with OA susceptibility. We found that rs639752 (dominant, OR = 2.03, 95% CI: 1.03-4.01, P = 0.038; over-dominant, OR = 2.00, 95% CI: 1.03-3.88, P = 0.037); rs520540 (dominant, OR = 2.03, 95% CI: 1.03-4.01, P = 0.038; over-dominant, OR = 2.00, 95% CI: 1.03-3.88, P = 0.037); rs602128 (dominant, OR = 2.03, 95% CI: 1.03-4.01, P = 0.038; over-dominant, OR = 2.01, 95% CI: 1.03-3.89, P = 0.037); and rs679620 (dominant, OR = 2.03, 95% CI: 1.03-4.01, P = 0.038; over-dominant, OR = 2.04, 95% CI: 1.05-3.96, P = 0.033) were associated with the increased risk of OA. Our results suggest that these SNPs may contribute to OA development, and could serve as molecular markers of OA susceptibility.

Association of ADAMTS4 and ADAMTS5 polymorphisms with musculoskeletal degenerative diseases: a systematic review and meta-analysis

“…ADAMTS4 and ADAMTS5, also known as aggrecanase-1 and aggrecanase-2, are two members of ADAMTSs family and have been shown to degrade the cartilage proteoglycanaggrecan [ 12 , 13 ]. A series of studies have suggested that variants of genes encoding ECM degrading enzymes were related with OA, such as matrix metalloproteinase (MMP)-1 [ 14–18 ], MMP-3 [ 14 , 19 , 20 ] and MMP-9 [ 17 ]. Strong associations between MMP-3, MMP-9 polymorphisms and risk of lumbar disc degeneration (LDD) were also indicated [ 21 , 22 ].…”

Association Between The Polymorphism of MMP-1 Gene with Knee Osteoarthritis Risk: A Meta-Analysis

“…Matrix metalloproteinase-1 (MMP-1)is produced by synovial cells, chondrocytes, and osteoblasts, which can degrade extracellular matrix collagen and mediate cartilage destruction [7][8]. The expression of MMPs has been shown to be affected by single nucleotide polymorphisms (SNPs) occurring in MMP gene promoters [9].These promoter polymorphisms have allele-speci c effects on the regulation of MMP gene transcription and are associated with the development and/or progression of some common diseases [3][4][5]. Matrix metalloproteinases secreted from chondrocytes are the main enzymes responsible for pathological cartilage destruction [6].Expression of MMP-1 is low in normal cells that leads to healthy cartilage remodeling.…”

Association between the polymorphism of MMP-1 gene with knee osteoarthritis risk: a meta-analysis

“…Knee OA is a common joint disease which is characterized by degeneration of the articular cartilage and subsequent subchondral bone changes. Knee OA is a combined result of environmental and genetic factors, while genetic factors account for nearly 50% of the risk of OA development [2].Although the underlying mechanisms remain unknown, many studies have shown that the occurrence of knee osteoarthritis is related to cytokines, including Matrix metalloproteinases (MMPs) family [3][4][5][6][7].…”

“…Matrix metalloproteinase-1 (MMP-1)is produced by synovial cells, chondrocytes, and osteoblasts, which can degrade extracellular matrix collagen and mediate cartilage destruction [7][8]. The expression of MMPs has been shown to be affected by single nucleotide polymorphisms (SNPs) occurring in MMP gene promoters [9].These promoter polymorphisms have allele-specific effects on the regulation of MMP gene transcription and are associated with the development and/or progression of some common diseases [3][4][5]. Matrix metalloproteinases secreted from chondrocytes are the main enzymes responsible for pathological cartilage destruction [6].Expression of MMP-1 is low in normal cells that leads to healthy cartilage remodeling.…”