Influence of variations across the MMP-1 and-3 genes on the serum levels of MMP-1 and-3 and disease activity in rheumatoid arthritis

Y. Chen, N. B. Nixon, P. T. Dawes, D. L. Mattey*

*Corresponding author for this work

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37 Citations (Scopus)

Abstract

Matrix metalloproteinases (MMPs) are involved in joint destruction in rheumatoid arthritis (RA), and are strongly associated with levels of inflammation. To understand the relationship between MMP-1 and-3 variants and MMP levels in RA, we investigated the genotypic and haplotypic relationships of the MMP-1 and-3 genes with circulating levels of these MMPs. The genotypes of single-nucleotide polymorphisms (SNPs) rs1799750 (1G/2G, MMP-1 promoter), rs495366 (G/A, intergene), rs679620 (A/G, MMP-3 coding region) and rs3025058 (5A/6A, MMP-3 promoter) were determined in 430 RA patients. Each polymorphism was associated with serum levels of MMP-1 (P trend <0.0001 for each SNP), with haplotype 1G-G-A-5A associated with the highest level. The intergenic and MMP-3 SNPs were associated with MMP-1 levels independent of the MMP-1 promoter SNP. The MMP-3 SNPs were associated with serum MMP-3 level (P trend <0.0001 for each SNP), and were each associated with mean time-averaged disease activity (DAS28) in patients followed up for 2 years (P=0.003). Our findings indicate that several closely linked polymorphisms in the MMP-1-MMP-3 loci have an important role in determining the circulating levels of these MMPs in RA, and that MMP-3 polymorphism is associated with the level of disease activity over time.

Original languageEnglish
Pages (from-to)29-37
Number of pages9
JournalGenes and Immunity
Volume13
Issue number1
DOIs
Publication statusPublished - Jan 2012
Externally publishedYes

Keywords

  • disease activity
  • matrix metalloproteinase
  • polymorphism
  • rheumatoid arthritis

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