基因组印记在儿童股骨头骨骺缺血性坏死发生中的关键作用机制及相关研究

Perthes disease is the osteonecrosis of children, it's closely related to developmental disorders of pediatric orthopedics. The etiology is unclear now, Many scholars have speculated that LCPD may be associated with genetic factor. Some genes like COL2A1, LEP, FGB, THBD, PEPD has been reported that was associated with LCPD. But did not find the exact link between them. In our preliminary studies, we also failed to find abnormal DNA levels in the whole group of patients Perthes, but detected a uniparental disomy(UPD) phenomenon occurred in all Perthes disease and found the imprinted gene(ACD and PSIMCT-1) in it. The imprinted gene and non-coding RNA(MIR1256) may be associated with the development of Perthes disease. Precise positioning of these products imprinted genes and their regulation, not only elaborate on the development of mechanisms Perthes disease, but also achieve diagnosis and treatment in the early stage, even reverse the progression of Perthes disease.

Perthes病即儿童股骨头坏死，是小儿骨科常见的一种与发育紧密相关的疾病，目前对于其发病机制还不明确。在遗传学及内分泌研究领域，国际上关于该病与基因联系的报道存在很大的差异性，往往不能代表整体人群。通过前期研究，我们并不能在Perthes病患儿人群中发现DNA水平的异常，但却检测出在所有纳入研究的Perthes病患儿中发生了单亲二倍体现象，并在这些片段里找到了印记基因。研究结果表明，印记基因ACD、PSIMCT-1以及非编码RNA（MIR1256）可能与Perthes病的发生发展有着至关重要的联系。通过全基因组芯片和DNA甲基化检测精确定位这些印记基因，建立perthes病的细胞以及动物模型，研究各分子事件之间的相互关系。既可以详细阐明Perthes病的发生发展机制，做到早期诊断，亦可利用去甲基化药物等技术手段为干预性治疗指明药物靶点，从而为阻断甚至逆转该病进程提供可能。

儿童股骨头骨骺缺血性坏死（Perthes病）是小儿骨科领域常见的疑难病之一，其确切的发病机制仍不明确。从分子遗传水平寻找Perthes病的病因，将有助于实现疾病的早期诊断及治疗，从而获得更佳的预后。我们在前期研究中通过基因芯片检测发现了位于染色体Xp21.1区域的异常基因-DMD，并通过qPCR检测发现其在Perthes病患者血样中表达降低；血供的异常被认为是Perthes病发病的关键因素，因此我们探究了异常基因DEPTOR对血管内皮细胞成血管功能的影响及机制，发现下调DEPTOR可以抑制内皮细胞的成血管能力，这在Perthes病发病中可能起到重要作用；通过对9例Perthes病及6例正常对照儿童的骨膜标本进行芯片检测，我们初步构建了lncRNA-mRNA、miRNA-mRNA及lncRNA- miRNA -mRNA的调控网络示意图，并筛选出了部分在此网络中具有关键作用的差异表达基因及信号通路。这将有助于加深对Perthes病病因及发病机制的认识，为将来对Perthes病的相关研究提供了新的思路。