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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

Genes & Immunity volume 13, pages 29–37 (2012)Cite this article

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.

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Acknowledgements

This work was funded by the Medical Research Council and the Haywood Rheumatism Research and Development Foundation. We thank Mrs Michelle Kirwan, Mrs Ann Barcroft (research nurses) and Mrs Janet Turner (research assistant) for their help with data collection and entry.

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Authors and Affiliations

  1. Institute of Science and Technology in Medicine, Keele University, Stoke-on-Trent, Staffordshire, UK

    Y Chen & D L Mattey

  2. Staffordshire Rheumatology Centre, Haywood Hospital, Stoke-on-Trent, Staffordshire, UK

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

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  1. Y Chen
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  2. N B Nixon
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Correspondence to D L Mattey.

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Chen, Y., Nixon, N., Dawes, P. et al. 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. Genes Immun 13, 29–37 (2012). https://doi.org/10.1038/gene.2011.46

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