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Rheumatology 2008 47(1):41-44; doi:10.1093/rheumatology/kem312
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© The Author 2007. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

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

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

Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.

Correspondence to: K. Ikari, Institute of Rheumatology, Tokyo Women's Medical University, 10-22 Kawada, Shinjuku, Tokyo 162-0054, Japan. E-mail: kikari{at}ior.twmu.ac.jp


  Abstract

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.

KEY WORDS: Rheumatoid arthritis, MMP-3, Association, Gene, IORRA

*S. Tsukahara and M. Shinozaki contributed equally to this work.

Submitted 22 June 2007; revised version accepted 26 October 2007.
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