Stefik Debora, Vranic Vladimir, Ivkovic Nemanja, Velikic Gordana, Maric Dusan M, Abazovic Dzihan, Vojvodic Danilo, Maric Dusica L, Supic Gordana
Institute for Medical Research, Military Medical Academy, Crnotravska 17, 11000 Belgrade, Serbia.
Clinic for Orthopedic Surgery and Traumatology, Military Medical Academy, Crnotravska 17, 11000 Belgrade, Serbia.
Biology (Basel). 2023 Mar 16;12(3):458. doi: 10.3390/biology12030458.
Osteoarthritis (OA) is a progressive inflammatory disease of synovial joints and a leading cause of disability among adults. Inflammation-related genes, including genes for Toll-like receptors (TLRs), are tightly controlled by several microRNAs that, in addition to their pivotal role in the epigenetic regulation of target genes, are ligands for TLR activation and downstream signaling. Thus, we evaluated the association between OA risk and genetic variants in TLR2, TLR3, TLR4, TLR7, TLR9, and microRNAs that regulate TLRs signaling miR146a, miR155, and miR196a2. Our study group consisted of 95 surgically treated OA patients and a control group of 104 healthy individuals. Genetic polymorphisms were determined using TaqMan real-time PCR assays (Applied Biosystems). Adjusted logistic regression analysis demonstrated that polymorphisms in TLR4 rs4986790 (OR = 2.964, = 0.006), TLR4 rs4986791 (OR = 8.766, = 0.00001), and TLR7 rs385389 (OR = 1.579, = 0.012) increased OA risk, while miR-196a2 rs11614913 (OR = 0.619, = 0.034) was significantly associated with decreased OA risk. Our findings indicate that polymorphisms in the TLR4 and TLR7 genes might increase OA risk and suggest a novel association of miR-196a2 polymorphism with decreased OA susceptibility. The modulation of TLRs and miRNAs and their cross-talk might be an attractive target for a personalized approach to OA management.
骨关节炎（OA）是一种滑膜关节的进行性炎症性疾病，也是成年人残疾的主要原因。包括Toll样受体（TLR）基因在内的炎症相关基因受到多种微小RNA的严格调控，这些微小RNA除了在靶基因的表观遗传调控中起关键作用外，还是TLR激活和下游信号传导的配体。因此，我们评估了TLR2、TLR3、TLR4、TLR7、TLR9基因变异与OA风险之间的关联，以及调控TLR信号传导的微小RNA miR146a、miR155和miR196a2与OA风险之间的关联。我们的研究组由95例接受手术治疗的OA患者和104名健康个体组成的对照组。使用TaqMan实时PCR检测法（应用生物系统公司）确定基因多态性。调整后的逻辑回归分析表明，TLR4 rs4986790（比值比=2.964，P=0.006）、TLR4 rs4986791（比值比=8.766，P=0.00001）和TLR7 rs385389（比值比=1.579，P=0.012）的多态性增加了OA风险，而miR-196a2 rs11614913（比值比=0.619，P=0.034）与OA风险降低显著相关。我们的研究结果表明，TLR4和TLR7基因的多态性可能会增加OA风险，并提示miR-196a2多态性与OA易感性降低之间存在新的关联。TLR和微小RNA的调节及其相互作用可能是OA个性化管理的一个有吸引力的靶点。
