Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, 100020, China.
Department of Cardiac Surgery, Children's Hospital Affiliated to Capital Institute of Pediatrics, No. 2 Yabao Road, Chao Yang District, Beijing, 100020, China.
BMC Med Genomics. 2021 Jan 6;14(1):4. doi: 10.1186/s12920-020-00848-0.
Congenital heart disease (CHD) is resulted from the interaction of genetic aberration and environmental factors. Imprinted genes, which are regulated by epigenetic modifications, are essential for the normal embryonic development. However, the role of imprinted genes in the etiology of CHD remains unclear.
After the samples were treated with bisulfate salt, imprinted genes methylation were measured by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. T test and One-way ANOVA were performed to evaluate the differences among groups. Odds ratios (ORs) were performed to evaluate the incidence risk of CHD in relation to methylation levels.
We investigated the alterations of imprinted gene germline differential methylation regions (gDMRs) methylation in patients with CHD. Eighteen imprinted genes that are known to affect early embryonic development were selected and the methylation modification genes were detected by massarray in 27 CHD children and 28 healthy children. Altered gDMR methylation level of 8 imprinted genes was found, including 2 imprinted genes with hypermethylation of GRB10 and MEST and 6 genes with hypomethylation of PEG10, NAP1L5, INPP5F, PLAGL1, NESP and MEG3. Stratified analysis showed that the methylation degree of imprinted genes was different in different types of CHD. Risk analysis showed that 6 imprinted genes, except MEST and NAP1L5, within a specific methylation level range were the risk factors for CHD CONCLUSION: Altered methylation of imprinted genes is associated with CHD and varies in different types of CHD. Further experiments are warranted to identify the methylation characteristics of imprinted genes in different types of CHD and clarify the etiologies of imprinted genes in CHD.
先天性心脏病（CHD）是由遗传异常和环境因素相互作用引起的。印迹基因受表观遗传修饰调控，对胚胎正常发育至关重要。然而，印迹基因在 CHD 发病机制中的作用尚不清楚。
用亚硫酸氢盐处理样本后，通过基质辅助激光解吸/电离飞行时间质谱法测量印迹基因的甲基化。采用 t 检验和单因素方差分析评估组间差异。采用比值比（OR）评估 CHD 与甲基化水平相关的发病风险。
我们研究了 CHD 患儿中印迹基因种系差异甲基化区域（gDMR）甲基化的改变。选择了已知影响早期胚胎发育的 18 个印迹基因，并通过质谱法在 27 名 CHD 患儿和 28 名健康儿童中检测了甲基化修饰基因。发现 8 个印迹基因的 gDMR 甲基化水平发生改变，包括 2 个印迹基因的 GRB10 和 MEST 呈超甲基化，6 个基因呈低甲基化，分别为 PEG10、NAP1L5、INPP5F、PLAGL1、NESP 和 MEG3。分层分析显示，不同类型 CHD 中印迹基因的甲基化程度不同。风险分析显示，在特定甲基化水平范围内，除 MEST 和 NAP1L5 外，6 个印迹基因是 CHD 的危险因素。
印迹基因的甲基化改变与 CHD 相关，并且在不同类型的 CHD 中有所不同。需要进一步的实验来确定不同类型 CHD 中印迹基因的甲基化特征，并阐明印迹基因在 CHD 中的病因学。
