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

摘要:

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（qRT-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①SFS 组和CFS 组1、3A、3 、2、4 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）。②SFS 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。

Abstract:

To explore the expression and clinical significance of epigenetic markers in the serum of the children with febrile seizures (FS). Methods RT-PCR and ELISA were used to measure the gene and protein ex-pressions of DNA methyltransferase 1 (DNMT1), DNMT3A, DNMT3B, histone methyltransferase EZH2 (EZH2), and histone deacetylase 4 (HDAC4) in 60 children with febrile seizures [30 with simple FS (SFS) and 30 with complex FS (CSF)] and 30 healthy controls. Results The gene expression levels of DNMT1, DNMT3A, DNMT3B, EZH2 and HDAC4 in the SFS and CFS groups were significantly higher than those in the control group (p < 0.05), while there were no significant differences between the SFS group and the CFS group (p > 0.05). The protein expressions of DNMT1, DNMT3A, DNMT3B, EZH2 and HDAC4 in the SFS and CFS groups were significantly higher than those in the 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, EZH2 and HDAC4 are highly expressed at the gene and proteinlevels in the serum of the children with SFS and CFS, which suggests that these epigenetic modifications may play important roles in the occurrence and development of FS and provides a reliable theoretical basis for further research of pathogenesis and prevention of FS.