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.
Rheumatology (Oxford). 2008 Jan;47(1):41-4. doi: 10.1093/rheumatology/kem312.
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.
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.
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).
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.
已发现启动子区域的双等位基因多态性-1612 ins/del A会影响基质金属蛋白酶-3（MMP-3）的产生。由于MMP-3在关节破坏中起特别关键的作用，因此MMP-3基因被认为是类风湿关节炎（RA）疾病严重程度的一个有趣的靶基因。我们试图确定MMP-3启动子多态性是否与日本RA患者的MMP-3血清滴度、疾病活动度及严重程度相关。
作为风湿病研究所类风湿关节炎观察性队列研究的一部分，从1504例RA患者中获取DNA样本。根据2006年春季的数据，通过酶免疫测定法可测得820例患者的血清MMP-3水平。对于162例患者，可使用Sharp/van der Heijde方法测量病程5年时的关节损伤评分。采用荧光标记片段分析法对-1612 ins/del A进行基因分型。通过线性回归分析，分析-1612 ins/del A多态性各基因型之间血清MMP-3水平和关节损伤评分的差异。
在包括疾病活动评分（P = 0.51）或健康评估问卷（P = 0.99）在内的患者特征方面，MMP-3各基因型之间未发现显著差异。观察到风险等位基因对血清MMP-3水平有显著影响（P = 0.038），而对影像学关节损伤无显著影响（P = 0.47）。
我们得出结论，MMP-3功能多态性与血清MMP-3滴度相关，但不是日本RA患者预后指标的直接预测因素。
