Stojanovic Sonja, Stoimenov Tatjana Jevtovic, Nedovic Jovan, Zivkovic Valentina, Despotovic Milena, Pavlovic Dusica
Institute "NiskaBanja", Faculty of Medicine, University of Nis, Nis, Serbia.
Department of Biochemistry, Faculty of Medicine, University of Nis, Nis, Serbia.
Clin Rheumatol. 2017 Jul;36(7):1479-1485. doi: 10.1007/s10067-017-3699-1. Epub 2017 Jun 1.
Matrix metalloproteinases (MMPs) are the key enzymes responsible for the joint destruction. Their activity is regulated by the level of proinflammatory cytokines. The aim of this study was to examine the impact of TNF-α G-308A polymorphism on MMP-9 levels in blood plasma (BP) and synovial fluid (SF) of patients with rheumatoid arthritis (RA) and their role in progression of joint destruction. One hundred thirty-four subjects were enrolled in this study. TNF-α G-308A polymorphism was determined using PCR-RFLP method. ELISA assay was used for the detection of MMP-9 activity in BP and SF. Joint damage was estimated by hands and feet radiography. Larsen score and annual changes in LS were used for quantitative evaluation of joint destruction and radiographic progression of disease. MMP-9 activity in BP and SF was significantly higher in RA compared to controls, as well as in SF of patients with erosive compared to nonerosive RA. Faster radiographic progression and increased MMP-9 activity in BP and SF were detected in the group A (GA or AA genotype carriers) compared to the group G (GG genotype carriers). However, statistical significance was revealed only for MMP-9 activity in SF (p < 0.05). MMP-9 activity in BP and SF is significantly higher in RA patients compared to patients with osteoarthritis. The presence of TNF-α-308A allele is associated with increased MMP-9 activity in SF of patients with early RA and may be a predictor of rapid radiographic progression of disease.
基质金属蛋白酶（MMPs）是导致关节破坏的关键酶。它们的活性受促炎细胞因子水平的调节。本研究的目的是检测肿瘤坏死因子-α（TNF-α）G-308A多态性对类风湿关节炎（RA）患者血浆（BP）和滑液（SF）中MMP-9水平的影响及其在关节破坏进展中的作用。134名受试者参与了本研究。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法测定TNF-α G-308A多态性。采用酶联免疫吸附测定（ELISA）法检测BP和SF中MMP-9的活性。通过手足X线摄影评估关节损伤。使用 Larsen 评分及 Larsen 评分的年度变化对关节破坏和疾病的影像学进展进行定量评估。与对照组相比，RA患者BP和SF中的MMP-9活性显著更高，与非侵蚀性RA患者相比，侵蚀性RA患者SF中的MMP-9活性也更高。与G组（GG基因型携带者）相比，A组（GA或AA基因型携带者）的影像学进展更快，BP和SF中的MMP-9活性增加。然而，仅SF中MMP-9活性具有统计学意义（p < 0.05）。与骨关节炎患者相比，RA患者BP和SF中的MMP-9活性显著更高。TNF-α -308A等位基因的存在与早期RA患者SF中MMP-9活性增加相关，可能是疾病影像学快速进展的一个预测指标。
