原发性帕金森病诊断、治疗的靶基因筛选  

Screening of target genes for diagnosis and treatment of primary Parkinson's disease

作　　者：李倩[1] 刘媛[1] 赵玉[1] 朱彧[2] 裘志军[3] 

机构地区：[1]天津市海河医院,天津300350 [2]天津市环湖医院 [3]天津医科大学总医院

出　　处：《山东医药》2017年第24期24-27,共4页Shandong Medical Journal

摘　　要：目的筛选原发性帕金森病(PD)诊断、治疗的靶基因。方法在基因表达综合(GEO)数据库中以"帕金森(Parkinson)"作为关键词,组织类型限定为中脑黑质,数据类型限定为基于基因芯片检测的基因表达谱数据,筛选出1个符合条件的数据集(GSE7621),该芯片数据包含9个正常(中脑无病变)样本(正常组)和16个原发性PD样本(PD组)。利用R编程语言的相关工具包对原始芯片数据进行预处理和差异表达基因的筛选。利用DAVID数据库对差异表达基因进行功能注释,并且构建差异表达基因的差异共表达网络及转录调控网络。将PC12细胞分为两组,分别为对照组和观察组,对照组常规培养,观察组给予50μmol/L 1-甲基-4-苯基吡啶离子(MPP)处理;处理24 h时,采用实时荧光定量PCR(qRT-PCR)法检测差异表达基因的相对表达量。结果正常组及PD组存在396个差异表达基因,相对于正常组,PD组存在下调基因229个、上调基因167个,主要富集功能为突触活动、多巴胺(DA)合成、神经元活动、突触传递、神经元投射、儿茶酚胺生物合成等。两组表达差异性最大的前十位基因分别为Zcchc6、Socs7、Ythdc1、Taf5、Spata13、Slc5a3、Heca、Epc2、Ddx23、Cdk2ap2。调控差异表达基因较多的前十个转录因子(TF)分别为AHR、DAND5、PSG1、SP1、PAX5、ARNT、MIA3、AP-2gamma、CREB1、AP-2alpha A。qRT-PCR结果显示,观察组与对照组Zcchc6、Socs7、Spata13、Slc5a3、Epc2、Cdk2ap2 mRNA表达量比较,P<0.05或<0.01;两组Ythdc1、Taf5、Heca、Ddx23 mRNA表达量比较P均>0.05。结论 Zcchc6、Socs7、Spata13、Slc5a3、Epc2、Cdk2ap2基因可能与原发性PD的发生、发展相关,可能作为其诊断及治疗的靶基因。Objective To screen the target genes for the diagnosis and treatment of primary Parkinson＇s disease （PD）.Methods In the GEO, ＂Parkinson＂ was used as the key word, the tissue type was defined as the midbrain substantia nigra, and the datum type was defined as the gene expression profile data based on gene chip detection.A qualitative data set was selected （GSE7621）, which contained 9 normal samples （control group） and 16 primary PD samples （PD group）.The original chip data were pretreated and the differentially expressed genes were screened by the relevant toolkit of R programming language.The DAVID database was used to annotate the differentially expressed genes, and we constructed the differential co-expression network and the transcriptional regulation network of differentially expressed genes.PC12 cells were divided into two groups： the control group and PD group.The PD group was treated with 50 μmol/L 1-methyl-4-phenylpyridine ion （MPP）.After 24 hour, real-time fluorescence quantitative PCR （qRT-PCR） was used to detect the relative expression of differentially expressed genes.Results There were 396 differentially expressed genes.Compared with the control group, 229 genes were down-regulated, while 167 genes were up-regulated in the PD group.They were mainly involved in the synaptic activity, DA synthesis, neuronal part, synaptic transmission, neuron projection, and catecholamine biosynthesis process.Zcchc6, Socs7, Ythdc1, Taf5, Spata13, Slc5a3, Heca, Epc2, Ddx23, and Cdk2ap2 were the top ten differentially expressed genes in the two groups.The top ten transcription factors （TF） were AHR, DAND5, PSG1, SP1, PAX5, ARNT, MIA3, AP-2gamma, CREB1, and AP-2alphaA.The difference in the expression of Zcchc6, Socs7, Spata13, Slc5a3, Epc2, and Cdk2ap2 was statistically significant between the two groups （P〈0.05 or P〈0.01）, while there were no statistical difference in the expression of Ythdc1, Taf5, Heca, and Ddx23 （all P〉0.05）.Conclusion Zcchc6, Socs7, Spata13, Slc5a3,

关 键 词：原发性帕金森病 靶基因筛选 基因表达综合数据库 差异共表达网络 

分 类 号：R742.5[医药卫生—神经病学与精神病学]