OPG/RANK/RANKL基因甲基化水平与激素性和酒精性股骨头坏死发病风险的关联性研究

Steroid and alcohol -induced osteonecrosis of the femoral head is a common clinical disease, which seriously endangers the patient's health and quality of life. However, only some of the patients suffered from femoral head necrosis when exposed to the risk factors(hormone and alcohol)under the same conditions, indicating that steroid and alcohol -induced osteonecrosis of the femoral head is a complex disease caused by the combination of genetic and environmental factors. The genetic susceptibility to the disease is important. DNA methylation is the earliest and most studied epigenetics mechanism, which is considered to be one of the causes of disease. On the basis of previous studies which have shown that the single nucleotide polymorphisms of the OPG/RANK/RANKL system were associated with the risk of hormonal and alcoholic necrosis of the femoral head, the aim of this study is to investigate the relationship between OPG/RANK/RANKL DNA methylation and gene transcription and protein expression. At the same time, we are to explore the association between OPG/RANK/RANKL DNA methylation and the single nucleotide polymorphism of the system. Combining with the previous research results, we will explore the important role of OPG/RANK/RANKL DNA methylation in the pathogenesis of steroid-induced and alcoholic osteonecrosis , which will provide the epigenetic basis for clinical prevention and treatment of steroid and alcohol -induced osteonecrosis of the femoral head.

激素性和酒精性股骨头坏死是临床常见病，多发病，严重危害患者的健康和生活质量。但同等条件暴露于激素和酒精危险因素下，只有部分患者发生股骨头坏死。说明激素性和酒精性股骨头坏死是遗传因素和环境因素共同作用而导致的复杂性疾病，该病具有遗传易感性。DNA甲基化是被人们认识最早，也是研究最多的表观遗传学机制，被认为是疾病的病因之一。在我们前期研究已经证实OPG/RANK/RANKL系统的单核苷酸多态性与激素性和酒精性股骨头坏死的发病风险相关的基础上，本实验旨在研究OPG/RANK/RANKL DNA甲基化与其基因转录和蛋白表达的关系，同时探讨与该系统单核苷酸多态性的关联性。结合我们前期研究成果，揭示OPG/RANK/RANKL DNA甲基化在激素性和酒精性骨坏死患者发病过程中的重要作用，为临床防治激素性和酒精性股骨头坏死提供表观遗传学依据。

激素性和酒精性股骨头坏死是临床常见病，多发病，严重危害患者的健康和生活质量。但同等条件暴露于激素和酒精危险因素下，只有部分患者发生股骨头坏死。说明激素性和酒精性股骨头坏死是遗传因素和环境因素共同作用而导致的复杂性疾病，该病具有遗传易感性。DNA甲基化是被人们认识最早，也是研究最多的表观遗传学机制，被认为是疾病的病因之一。在我们前期研究已经证实OPG/RANK/RANKL系统的单核苷酸多态性与激素性和酒精性股骨头坏死的发病风险相关的基础上，本实验旨在研究OPG/RANK/RANKL DNA甲基化与其基因转录和蛋白表达的关系，同时探讨该系统甲基化与股骨头坏死发病之间关联性。结合我们前期研究成果，揭示OPG/RANK/RANKL DNA甲基化在激素性和酒精性骨坏死患者发病过程中的重要作用，为临床防治激素性和酒精性股骨头坏死提供表观遗传学依据。.在本实验中，我们使用MassARRAY系统分析了激素性股骨头坏死患者和酒精性股骨头坏死患者与健康对照组各50例血清中OPG、RANK和RANKL基因的甲基化状态。观察到DNA甲基化的显著变化。发现多个候选基因的高甲基化CpG位点。推测其与激素性和酒精性股骨头坏死发病风险密切相关，可能作为疾病早期筛查和诊断的有效靶点。

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