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Effect of matrix metalloproteinase-3 functional SNP on serum matrix metalloproteinase-3 level and outcome measures in Japanese RA patients.

Tsukahara S, Shinozaki M, Ikari K, Mochizuki T, Inoue E, Tomatsu T, Hara M, Yamanaka H, Kamatani N, Momohara S

Institute of Rheumatology, Tokyo Women's Medical University, 10-22 Kawada, Shinjuku, Tokyo 162-0054, Japan.

OBJECTIVE: A bi-allelic polymorphism on the promoter region, -1612 ins/del A, was found to influence the production of MMP-3. Since MMP-3 plays a particularly pivotal role in joint destruction, the MMP-3 gene is thought to be an interesting target gene of disease severity in RA. We attempt to determine whether the MMP-3 promoter polymorphism is associated with serum titre of MMP-3, disease activity and severity in Japanese RA patients. METHODS: DNA samples were obtained from 1504 RA patients as part of the Institute of Rheumatology Rheumatoid Arthritis observational cohort study. From the 2006 spring data, serum MMP-3 levels of 820 patients were available by enzyme immunoassay. Joint damage score at 5-yr disease duration could be measured using the Sharp/van der Heijde method in 162 patients. Genotyping of -1612 ins/del A was performed using fluorescent-labelled fragment analysis. Differences in serum MMP-3 level and joint damage score among genotypes of -1612 ins/del A polymorphism were analysed by linear regression analysis. RESULTS: No significant differences were found among MMP-3 genotypes on patient characteristics including disease activity score (P = 0.51) or health assessment questionnaire (P = 0.99). A significant effect of risk allele on serum MMP-3 level was observed (P = 0.038), while no significant effect was observed on radiographic joint damage (P = 0.47). CONCLUSION: We conclude that MMP-3 functional polymorphism is associated with serum MMP-3 titre, but is not a direct predictor for outcome measures in Japanese RA patients.

Published 13 December 2007 in Rheumatology (Oxford), 47(1): 41-4.
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