Association of matrix metalloproteinase 3 promoter genotype with disease outcome in rheumatoid arthritis.
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.
Mattey
D L
DL
Staffordshire Rheumatology Centre, University Hospital of North Staffordshire, The Haywood, Staffordshire, UK. d.l.mattey@keele.ac.uk
Nixon
N B
NB
Dawes
P T
PT
Ollier
W E R
WE
Hajeer
A H
AH
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging* / Q000235:genetics*; D017931:DNA Primers; D018450:Disease Progression; D005838:Genotype; D006801:Humans; D019278:Matrix Metalloproteinase 3 / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011859:Radiography; D018709:Statistics, Nonparametric; D006113:United Kingdom
D017931:DNA Primers; D019278:Matrix Metalloproteinase 3