热性惊厥患儿血清中表观遗传标志物的表达及临床意义

Expression and significance of epigenetic markers in serum of children with febrile seizures

目的分析热性惊厥(FS)患儿血清中DNA甲基转移酶1、3A、3B(DNMT1、DNMT3A、DNMT3B)、组蛋白甲基转移酶EZH2(EZH2)及组蛋白去乙酰化酶4(HDAC4)的变化情况,探讨其在FS疾病中的临床意义。方法选取60例FS患儿,其中包括30例单纯型FS(SFS)和30例复杂型FS(CFS)。另选取30例正常健康体检儿童为正常对照组,采用实时荧光定量聚合酶链反应(q RT-PCR)和酶联免疫吸附实验(ELISA)检测比较3组间3种酶基因和蛋白之间的表达水平变化。结果 (1)SFS组和CFS组DNMT1、DNMT3A、DNMT3B、EZH2、HDAC4基因表达均高于正常对照组,差异有统计学意义(P<0.05);SFS组与CFS组之间比较,差异无统计学意义(P>0.05)。(2)SFS组和CFS组DNMT1、DNMT3A、DNMT3B、EZH2、HDAC4蛋白表达水平均高于正常对照组,差异有统计学意义(P<0.05);SFS组与CFS组之间比较,差异无统计学意义(P>0.05)。结论SFS和CFS组患儿血清中DNMT1、DNMT3A、DNMT3B、EZH2和HDAC4基因及蛋白水平均呈现高表达模式,提示表观遗传修饰在FS中的发生发展过程中发挥着重要作用,为深入研究FS的致病机制及防治FS提供了实验依据。

Objective To explore the expression and clinical significance of epigenetic markers in the serum ofthe children with febrile seizures(FS).Methods RT-PCR and ELISA were used to measure the gene and protein expressions of DNA methyltransferase1(DNMT1),DNMT3A,DNMT3B,histone methyltransferase EZH2(EZH2),andhistone deacetylase4(HDAC4)in60children with febrile seizures[30with simple FS(SFS)and30with complexFS(CSF)]and30healthy controls.Results The gene expression levels of DNMT1,DNMT3A,DNMT3B,EZH2andHDAC4in the SFS and CFS groups were significantly higher than those in the control group(P<0.05),while therewere no significant differences between the SFS group and the CFS group(P>0.05).The protein expressions ofDNMT1,DNMT3A,DNMT3B,EZH2and HDAC4in the SFS and CFS groups were significantly higher than those inthe control group(P<0.05);there were no significant differences between the SFS group and the CFS group(P>0.05).Conclusions DNMT1,DNMT3A,DNMT3B,EZH2and HDAC4are highly expressed at the gene and protein levels in the serum of the children with SFS and CFS,which suggests that these epigenetic modifications may playimportant roles in the occurrence and development of FS and provides a reliable theoretical basis for further researchof pathogenesis and prevention of FS.