Effect of matrix metalloproteinase-3 functional SNP on serum matrix metalloproteinase-3 level and outcome measures in Japanese RA patients
Effect of matrix metalloproteinase-3 functional SNP on serum matrix metalloproteinase-3 level and outcome measures in Japanese RA patients
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DOI：
10.1093/rheumatology/kem312
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发表时间：
2008-01-01
期刊：
影响因子：
5.5
通讯作者：
Momohara, S.
中科院分区：
文献类型：
--
作者：
Tsukahara, S.;Shinozaki, M.;Momohara, S.
Objective.发现启动子区域上的双等位基因多态性，-1612 ins/del A，影响MMP-3的产生。由于MMP-3在关节破坏中起着特别关键的作用，MMP-3基因被认为是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、疾病活动性和严重程度相关。从1504例RA患者中获得DNA样本，作为风湿性关节炎观察性队列研究的一部分。从2006年春季的数据，820例患者的血清MMP-3水平通过酶免疫法。在162例患者中，可使用Sharp/货车der Heijde方法测量5年病程时的关节损伤评分。使用荧光标记片段分析进行-1612 ins/del A的基因分型。采用线性回归分析-1612 ins/del A多态性基因型与血清MMP-3水平及关节损伤评分的差异。MMP-3基因型之间在疾病活动性评分（P=0.51）或健康评估问卷（P=0.99）等患者特征方面无显著差异。危险等位基因对血清MMP-3水平有显著影响（P=0.038），而对X线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患者结局指标的直接预测因子。
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.