子痫前期胎盘组织甲基化情况及免疫相关候选基因分析

Methylation of placental tissue in cases with preeclampsia and analysis on immunerelated candidate genes

目的:探讨子痫前期(PE)胎盘组织甲基化情况及分析免疫相关候选基因。方法:应用全基因组甲基化芯片检测早发型PE(EOPE)、晚发型PE(LOPE)及对照组胎盘组织,分析其主要参与的信号通路及生物学功能,筛选参与PE的免疫相关候选基因进行焦磷酸测序。结果:EOPE组总体平均甲基化程度较高,与正常对照组比较EOPE和LOPE组筛选出的差异基因主要参与调控多细胞生物过程、生长发育过程、多细胞生物发育过程等;焦磷酸测序显示3组间KIR2DL4基因甲基化差异无统计学意义(P>0.05)。TNFAIP8的位点1中,EOPE组和对照组相比及EOPE组和LOPE组相比差异都有统计学意义(P<0.05);而TNFAIP8的位点2中,仅EOPE组和LOPE组相比差异有统计学意义(P<0.05)。结论:PE与正常胎盘组织中差异性甲基化基因主要参与调控生长发育过程,TNFAIP8在早发型胎盘组织中明显低甲基化。

Objective： To explore methylation of placental tissue in eases with preeclampsia and analyze immune - related candi- date genes. Methods： Whole genome methylation microarray was used to detect the placental tissues of cases with early - onset preeclamp- sia, cases with late -onset preeclampsia and normal cases （control group） ; the mainly involved signal pathway and biological function were analyzed, immune - related candidate genes were screened to conduct pyrosequencing, Results. The total methylation level in early - onset preeclampsia group was relatively high, compared with control group, the differential genes screened out in early -onset preeclampsia group and late - onset preeclampsia group mainly participated in regulating multicellular organismal process, growth and development and multicel- lular biological development; pyrosequencing showed there was no statistically significant difference in methylation of KIR2DIA gene among the three groups （ P 〉 0. 05 ） . There were statistically significant differences in locus 1 of TNFAIP8 gene between early - onset preeclampsia group and control group, late - onset preeclampsia group, respectively （P 〈 0. 05 ） ; there was statistically significant difference in locus 2 of TNFAIP8 gene between early - onset preeclampsia group and late - onset preeclampsia group （ P 〈 0. 05 ） . Conclusion ： The differential methylation genes between preeclampsia and normal placenta are mainly involved in regulating growth and development, methylation level of TNFAIP8 gene in placental tissue of cases with early - onset preeclampsia is low.