Brain Center University Medical Center Utrecht, Department of Psychiatry, Utrecht University, A01.468, PO Box 85500, 3508, GA, Utrecht, The Netherlands.
Brain Center University Medical Center Utrecht, Department of Translational Neuroscience, Utrecht University, Utrecht, The Netherlands.
Clin Epigenetics. 2019 May 16;11(1):80. doi: 10.1186/s13148-019-0680-7.
DNA methylation has recently been identified as a mediator between in utero famine exposure and a range of metabolic and psychiatric traits. However, genome-wide analyses are scarce and cross-sectional analyses are hampered by many potential confounding factors. Moreover, causal relations are hard to identify due to the lack of controlled experimental designs. In the current study, we therefore combined a comprehensive assessment of genome-wide DNA methylation differences in people exposed to the great Chinese famine in utero with an in vitro study in which we deprived fibroblasts of nutrition.
We compared whole blood DNA methylation differences between 25 individuals in utero exposed to famine and 54 healthy control individuals using the HumanMethylation450 platform. In vitro, we analyzed DNA methylation changes in 10 fibroblast cultures that were nutritionally deprived for 72 h by withholding fetal bovine serum.
We identified three differentially methylated regions (DMRs) in four genes (ENO2, ZNF226, CCDC51, and TMA7) that were related to famine exposure in both analyses. Pathway analysis with data from both Chinese famine samples and fibroblasts highlighted the nervous system and neurogenesis pathways as the most affected by nutritional deprivation.
The combination of cross-sectional and experimental data provides indications that biological adaptation to famine leads to DNA methylation changes in genes involved in the central nervous system.
DNA 甲基化最近被确定为胎儿期饥荒暴露与一系列代谢和精神特征之间的中介。然而，全基因组分析很少，横断面分析受到许多潜在混杂因素的阻碍。此外，由于缺乏对照实验设计，因果关系难以确定。在本研究中，我们将对经历过中国大饥荒的人群进行全基因组 DNA 甲基化差异的综合评估，并结合体外研究，即在体外剥夺成纤维细胞的营养。
我们使用 HumanMethylation450 平台比较了 25 名胎儿期暴露于饥荒的个体和 54 名健康对照个体的全血 DNA 甲基化差异。在体外，我们通过剥夺胎牛血清来分析 10 个成纤维细胞培养物中 72 小时的营养剥夺引起的 DNA 甲基化变化。
我们在两个分析中都发现了与饥荒暴露相关的四个基因（ENO2、ZNF226、CCDC51 和 TMA7）中的三个差异甲基化区域（DMRs）。来自中国饥荒样本和成纤维细胞的数据的通路分析突出了神经系统和神经发生途径是受营养剥夺影响最严重的途径。
横断面和实验数据的结合表明，对饥荒的生物适应性导致中枢神经系统相关基因的 DNA 甲基化变化。
