外周血中脑源性神经营养因子基因启动子区甲基化调控与帕金森病的相关性  

Correlation between methylation of peripheral brain derived neurotrophic factor gene promoter region and Parkinson′s disease

作　　者：赵艳青 袁瑞 王欣琪 王丽珍[2,3] 杨志甫[1] Zhao Yanqing;Yuan Rui;Wang Xinqi;Wang Lizhen;Yang Zhifu(Department of Neurology,First Affiliated Hospital,Inner Mongolia University of Science and Technology,Baotou 014000,Inner Mongolia Autonomous Region,China;Department of Pathology,School of Basic Medicine and Forensic Medicine,Inner Mongolia University of Science and Technology,Baotou 014000,Inner Mongolia Autonomous Region,China;Department of Pathology,First Affiliated Hospital,Baotou Medical College,Inner Mongolia University of Science and Technology,Baotou 014000,Inner Mongolia Autonomous Region,China)

机构地区：[1]内蒙古科技大学包头医学院第一附属医院神经内科,内蒙古包头014000 [2]内蒙古科技大学包头医学院基础医学与法医学院病理教研室,内蒙古包头014000 [3]内蒙古科技大学包头医学院第一附属医院病理科,内蒙古包头014000

出　　处：《中华老年多器官疾病杂志》2025年第4期265-270,共6页Chinese Journal of Multiple Organ Diseases in the Elderly

基　　金：内蒙古自治区自然科学基金(2021MS08053);内蒙古自治区卫生健康科技计划项目(202201422);包头医学院青年科技人才发展计划(BYJJ-DXK 2022042)。

摘　　要：目的观察帕金森病(PD)患者外周血脑源性神经营养因子(BDNF)基因启动子区甲基化及其表达水平的改变,分析二者的相关性,从表观遗传调控的角度探讨PD的发生机制。方法选择2020年9月至2023年10月于包头医学院第一附属医院就诊的54例PD患者(PD组)和51例同期健康体检人(对照组)为研究对象,采用甲基化特异性聚合酶链式反应(MS-PCR)检测外周血BDNF基因启动子区的甲基化状态;采用实时定量聚合酶链式反应(Q-PCR)测定外周血中BDNF mRNA表达水平。采用SPSS 20.0统计软件进行数据分析。根据数据类型,组间比较分别采用t检验或Mann-Whitney U检验。采用Spearman秩相关分析BDNF基因启动子区甲基化水平与mRNA表达的相关性。采用Pearson相关分析BDNF mRNA表达水平与帕金森病综合评价量表(UPDRS)总评分、UPDRS运动症状评分、UPDRS非运动症状评分的相关性。采用二元logistic回归模型分析PD发病的影响因素。结果PD组外周血BDNF启动子区甲基化率显著高于对照组,且中晚期PD患者外周血BDNF启动子区甲基化率高于早期PD患者,差异有统计学意义(P<0.05)。PD组患者外周血BDNF表达水平低于对照组,且中晚期PD患者外周血BDNF表达水平低于早期PD患者,差异有统计学意义(P<0.05)。PD组外周血BDNF mRNA表达水平与BDNF启动子区甲基化水平呈显著负相关(r=-0.928;P<0.001),与UPDRS总评分、UPDRS运动症状评分、UPDRS非运动症状评分呈负相关(r=-0.461,-0.429,-0.298;P<0.05)。二元logistic回归分析显示,BDNF启动子区甲基化状态是PD发病的一个危险因素(OR=3.887,95%CI 1.035~14.597;P=0.044),甘油三酯是PD发病的保护因素(OR=0.392,95%CI 0.155~0.997;P=0.049)。结论PD患者外周血BDNF启动子区呈异常高甲基化,BDNF基因mRNA表达下调,且两者存在负相关,提示BDNF启动子区异常高甲基化可能通过下调其表达而参与PD的发生发展。Objective To observe the alterations in the methylation of brain derived neurotrophic factor(BDNF)gene promoter region and its expression level in peripheral blood of Parkinson′s disease(PD)patients,and analyze their correlation in order to explore the pathogenesis of PD from the perspective of epigenetic regulation.Methods A total of 54 PD patients(PD group)admitted to the First Affiliated Hospital of Baotou Medical College from September 2020 to October 2023 were enrolled,and another 51 healthy individuals who taking physical examination in the hospital during same period served as control group.Methylation-specific polymerase chain reaction(MS-PCR)was applied to assess the methylation status of peripheral BDNF promoter,and quantitative real-time polymerase chain reaction(Q-PCR)was conducted to determine the mRNA expression of BDNF in peripheral blood.SPSS statistics 20.0 was used for data analysis.Depending on data type,t test or Mann-Whitney U test was used for inter-group comparison.Spearman rank correlation analysis was employed to analyze the correlation between the methylation level of BDNF gene promoter region and mRNA expression.Pearson correlation analysis was utilized to analyze the correlation of BDNF mRNA level with the total score,motor symptom score and non-motor symptom score of unified Parkinson′s disease rating scale(UPDRS).Binary logistic regression model was built to identify the influencing factors for PD incidence.Results The methylation rate of peripheral BDNF promoter was significantly higher in the PD group than the control group,and the rate was also higher in the PD patients in mid-to-late stage than those in early stage(P<0.05).The PD patients exhibited significantly lower expression level of peripheral blood BDNF than the control group,and the level was notably lower in mid-to-late-stage PD patients than the early-stage PD patients(P<0.05).In PD group,the mRNA level of BDNF in peripheral blood was negatively correlated with its promoter methylation level(r=-0.928;P<0.001),and the

关 键 词：帕金森病 表观遗传修饰 DNA甲基化 神经营养因子 脑源性 

分 类 号：R742.5[医药卫生—神经病学与精神病学] R592[医药卫生—临床医学]