中国临床医学2025，Vol.32Issue(1)：65-71,7.DOI:10.12025/j.issn.1008-6358.2025.20241021
子痫前期胎盘中印记差异甲基化区域特征分析
Characteristics of imprinted differentially methylated regions in preeclampsia placenta
摘要
Abstract
Objective To investigate the characteristics of imprinted differentially methylated regions(iDMRs)in placentas and their correlation with preeclampsia(PE).Methods A total of 43 healthy pregnant women(control group)and 33 pregnant women with PE(PE group)at Shanghai Putuo Maternity and Infant Hospital and International Peace Maternal and Child Health Hospital,Shanghai Jiao Tong University School of Medicine from September 2021 to September 2023 were selected.A total of 3 362 CpG sites in 62 iDMRs were analyzed in 76 placenta and 5 maternal blood samples using BisCap targeted bisulfite resequencing(BisCap-seq)assays.The CpG sites in the CpG islands of the iDMRs were assessed for their methylation levels and methylation linkage disequilibrium(MLD).Imprinted methylation haplotype blocks(iMHBs)were constructed based on MLD.The methylation levels and variablility of CpG sites and iMHBs were compared among the healthy placenta,PE placenta and blood samples.Results The CpG sites in the CpG islands of the iDMRs exhibited intermediate methylation,with adjacent sites displaying high MLD(methylation levels:0.35-0.65,D'＞0.8).A total of 185 iMHBs were constructed using these coupled CpG sites,60 placenta-specific iMHBs and 38 somatic iMHBs were found to be differentially methylated in the placenta compared with maternal blood(Padj＜0.05).Twenty-seven iMHBs were identified with differentially variable methylation patterns in the placenta.The iMHBs methylation was unchanged in the PE placentas compared to the healthy placentas.Twenty-seven differentially methylated cytosines(DMCs)were identified outside the iMHBs structure,among which the methylation levels of 19 CpG sites showed statistically significant differences between the PE group and the control group(Padj＜0.05).The quantitative results of placental compositions of maternal plasma cell-free DNA(cfDNA)using placenta-specific haplotype(PSH)were highly correlated with those estimated by a deconvolution methodology(r=0.973,P＜0.01).Conclusions The genomic imprinting features in the PE placentas were obvious,and PSH could be a potential marker of the placenta to quantify the placental compositions of maternal plasma cfDNA.关键词
印记基因/印记差异甲基化区域/印记甲基化单倍型区块/胎盘/子痫前期Key words
imprinted gene/imprinted differentially methylated region/imprinted methylation haplotype block/placenta/preeclampsia分类
医药卫生引用本文复制引用
汤慧君,郏晓骏,赵欣之,叶伟萍..子痫前期胎盘中印记差异甲基化区域特征分析[J].中国临床医学,2025,32(1):65-71,7.基金项目
上海市自然科学基金(22ZR1467800),上海市普陀区卫生健康系统科技创新项目(ptkwws202122).Supported by Natural Science Foundation of Shanghai(22ZR1467800)and Science and Technology Innovation Project of Shanghai Putuo Health Commission(ptkwws202122). （22ZR1467800）
