DNA甲基化与羟甲基化在帕金森病患者中的意义及与TET蛋白的关系  

Significance of DNA methylation and hydroxymethylation in patients with Parkinson’s disease and their relationship with TET protein

作　　者：周亚丽 王丽娜 赵丰丽 ZHOU Yali;WANG Lina;ZHAO Fengli(Yuncheng Central Hospital,Yuncheng 044000,China)

机构地区：[1]运城市中心医院,山西运城044000

出　　处：《中国实用神经疾病杂志》2025年第3期336-340,共5页Chinese Journal of Practical Nervous Diseases

基　　金：2021年山西省医学重点科研计划项目(编号:2020XM59)。

摘　　要：目的分析DNA甲基化、羟甲基化在帕金森病患者中的意义及其与TET蛋白之间的关联。方法纳入2021-10—2023-10于运城市中心医院神经内科住院的帕金森病患者106例以及同期健康体检者106例,所有帕金森病患者分为预后良好组和预后不良组。收集所有研究对象的外周血,提取全基因组DNA,采用双抗体夹心酶联免疫吸附法(ELISA)法进行5-mC以及5-hmC百分比的测定;提取PBMC,采用qPCR进行TET1、TET2、TET3的mRNA表达水平的测定。采用Spearman相关性分析TET1、TET2、TET3的表达水平与5-mC及5-hmC的相关性,ROC曲线分析TET1、TET2对帕金森病患者预后的预测价值。结果与对照组相比,帕金森病患者血浆5-mC以及5-hmC水平均显著升高,TET1、TET2、TET3表达水平均显著升高,差异均有统计学意义(P<0.05)。Pearson相关分析显示,帕金森病患者TET1、TET2、TET3与5-mC水平之间无显著相关性,TET1、TET2表达水平与5-hmC呈显著正相关(r=0.573、0.647,P<0.01),TET3表达水平与5-hmC无明显相关性。ROC曲线提示,TET1、TET2预测不良预后的风险的AUC值分别为0.861、0.887。结论帕金森病患者DNA甲基化、羟甲基化水平显著升高,TET1、TET2介导的5-hmC表达水平上调从而促进帕金森病的发生与进展,可成为进一步研究帕金森病的重要标志物。Objective To analyze the significance of DNA methylation and hydroxymethylation in patients with Parkinson’s disease,and the correlation between DNA methylation and TET protein.Methods A total of 106 patients with Parkinson’s disease who were hospitalized in the Department of Neurology,Yuncheng Central Hospital from October 2021 to October 2023 and 106 healthy subjects during the same period were included.All Parkinson’s disease patients were divided into the good prognosis group and the poor prognosis group.Peripheral blood of all subjects was collected,whole genome DNA was extracted,and 5-mC and 5-hmC percentage were determined by double-antibody sandwich enzyme-linked immunosorbent assay(ELISA).PBMC was extracted and the mRNA expression levels of TET1,TET2 and TET3 were determined by qPCR.Spearman correlation analysis was used to compare the expression levels of TET1,TET2 and TET3 with 5-mC and 5-hmC.The predictive value of TET1 and TET2 in prognosis of Parkinson’s disease patients was analyzed by receiver operating characteristic curve(ROC curve).Results Compared with control group,the plasma levels of 5-mC and 5-hmC in PD patients were significantly increased,and the expression levels of TET1,TET2 and TET3 were significantly increased,with statistical significance(P<0.05).Pearson correlation analysis showed that there was no significant correlation between TET1,TET2,TET3 and 5-mC levels in Parkinson’s disease patients,and the expression levels of TET1 and TET2 were significantly positively correlated with 5-hmC(r=0.573,0.647,P<0.01),while the expression level of TET3 was not significantly correlated with 5-hmC.ROC curve indicated that the AUC values of TET1 and TET2 in predicting the risk of adverse prognosis were 0.861 and 0.887,respectively.Conclusion DNA methylation and hydroxymethylation levels are significantly increased in patients with Parkinson’s disease,and TET1 and TET2-mediated 5-hmC expression levels are up-regulated,which promotes the occurrence and progression of Parkinson’s disea

关 键 词：帕金森病 甲基化 羟甲基化 TET蛋白 预后 

分 类 号：R742.5[医药卫生—神经病学与精神病学]