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Association of matrix metalloproteinase 3 promoter genotype with disease outcome in rheumatoid arthritis

Genes & Immunity volume 5, pages 147–149 (2004)Cite this article

Abstract

Matrix metalloproteinases (MMPs) are implicated in joint destruction in rheumatoid arthritis (RA). We investigated whether the 5A/6A polymorphism within the MMP-3 (stromelysin-1) gene promoter region is associated with disease outcome in 254 patients with established RA. Patients homozygous for the MMP-3 6A allele had more radiographic damage (measured by Larsen score) than those with other genotypes (109.8 vs 91.1, P=0.04). Patients with the 6A/6A genotype also had more functional impairment and higher serum proMMP-3 levels, although only the latter was significant (P=0.002). A possible association was found between homozygosity for the 6A allele and carriage of the RA-associated HLA-DRB1 shared epitope (SE). Combination of these factors was associated with more severe disease than the SE alone. The data suggest that the MMP-3 6A/6A genotype is associated with worse RA outcome, and that this genotype may have an additive effect with the SE on disease severity.

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Acknowledgements

This work was supported by the Haywood Rheumatism Research and Development Foundation and the Arthritis Research Campaign.

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Authors and Affiliations

  1. Staffordshire Rheumatology Centre, University Hospital of North Staffordshire, The Haywood, Staffordshire, UK

    D L Mattey, N B Nixon & P T Dawes

  2. Centre for Integrated Genomic Medical Research, Manchester University Medical School, Manchester, UK

    W E R Ollier & A H Hajeer

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  1. D L Mattey
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  2. N B Nixon
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  3. P T Dawes
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  4. W E R Ollier
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  5. A H Hajeer
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Correspondence to D L Mattey.

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Mattey, D., Nixon, N., Dawes, P. et al. Association of matrix metalloproteinase 3 promoter genotype with disease outcome in rheumatoid arthritis. Genes Immun 5, 147–149 (2004). https://doi.org/10.1038/sj.gene.6364050

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