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

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.

• Authors: D L Mattey, N B Nixon, P T Dawes, W E R Ollier, A H Hajeer
• Journal: Genes and immunity (Genes Immun) Vol. 5 Issue 2 Pg. 147-9 (Mar 2004) ISSN: 1466-4879 [Print] England
• PMID: 14712311 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA Primers
• Matrix Metalloproteinase 3

Topics

• Adult
• Aged
• Analysis of Variance
• Arthritis, Rheumatoid (diagnostic imaging, genetics)
• DNA Primers
• Disease Progression
• Genotype
• Humans
• Matrix Metalloproteinase 3 (blood, genetics)
• Middle Aged
• Polymerase Chain Reaction
• Promoter Regions, Genetic (genetics)
• Radiography
• Statistics, Nonparametric
• United Kingdom