Jiang Yongqing, Yao Meng, Liu Qingpeng, Zhou Changwei
Arthritis Res Ther. 2013 Jan 5;15(1):R3. doi: 10.1186/ar4129.
A body of studies suggests the role of osteopontin (OPN) in onset and development of osteoarthritis (OA), however, the association between OPN polymorphisms and OA susceptibility as well as its clinical features has not been reported.
A total of 750 patients with primary knee OA and 794 healthy volunteer were enrolled as controls. Both OA and control groups were interviewed to obtain demographic and clinical data. Three polymorphisms of OPN gene, namely, -156GG/G, -443C/T and -66T/G were determined. The levels of the full length and the thrombin-cleaved OPN in synovial fluid (SF) from OA subjects were measured.
We found the polymorphisms of the -443C/T and the -66/T/G were significantly associated with the OA risk and the radiographic severity. The -443TT and -66GG showed protective effect against developing OA and were associated with lower Kellgren-Lawrence grade. Besides, the polymorphisms of -443C/T and -66T/G significantly affected the thrombin-cleaved OPN levels in SF from OA subjects. Subjects with -443TT and -66GG genotypes had lower thrombin-cleaved OPN levels in SF. The thrombin-cleaved OPN levels in SF were positively correlated to the radiographic severity of OA.
Our findings suggest that certain OPN gene polymorphisms may be used as molecular markers for the susceptibility and severity of OA.
大量研究表明骨桥蛋白(OPN)在骨关节炎(OA)的发病和发展中起作用,然而,OPN基因多态性与OA易感性及其临床特征之间的关联尚未见报道。
共纳入750例原发性膝关节OA患者和794名健康志愿者作为对照。对OA组和对照组进行访谈以获取人口统计学和临床数据。测定OPN基因的三个多态性位点,即-156GG/G、-443C/T和-66T/G。测量OA患者滑液(SF)中全长OPN和凝血酶切割型OPN的水平。
我们发现-443C/T和-66/T/G多态性与OA风险和影像学严重程度显著相关。-443TT和-66GG对OA发病具有保护作用,并与较低的Kellgren-Lawrence分级相关。此外,-443C/T和-66T/G多态性显著影响OA患者SF中凝血酶切割型OPN的水平。-443TT和-66GG基因型的患者SF中凝血酶切割型OPN水平较低。SF中凝血酶切割型OPN水平与OA的影像学严重程度呈正相关。
我们的研究结果表明,某些OPN基因多态性可能作为OA易感性和严重程度的分子标志物。