DNA methylation profiles of elderly individuals subjected to indentured childhood labor and trauma.

DNA methylation profiles of elderly individuals subjected to indentured childhood labor and trauma.
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遭受童年契约劳动和创伤的老年人的 DNA 甲基化谱。

DOI:
10.1186/s12881-017-0370-2
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发表时间:
2017-02-27
影响因子:
--
通讯作者:
Burri A
Burri A
中科院分区:
医学4区
文献类型:
--
作者:
Marinova Z;Maercker A;Küffer A;Robinson MD;Wojdacz TK;Walitza S;Grünblatt E;Burri A

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童年创伤与日后生活中更容易遭受精神和躯体疾病有关。 DNA 甲基化等表观遗传修饰是一种潜在机制,通过它可以解释这种长期的损害/后果。本研究的目的是调查童年创伤是否与老年时的长期 DNA 甲基化改变有关。我们评估了一群遭受过严重童年逆境的前契约童工(“Verdingkinder”)的全基因组 DNA 甲基化谱(N = 30;M 年龄 = 75.9 岁),并将他们与具有相似人口特征的对照组(N = 15,M 年龄 = 72.8 岁)进行比较。 DNA 从口腔上皮细胞中分离出来,并与 Illumina Infinium 450 k DNA 甲基化阵列杂交,该阵列覆盖了 485,000 个甲基化位点。在考虑批次效应、年龄、性别和多重测试后,在两组之间确定了 71 个差异甲基化 CpG 位置。它们被注释为参与神经元投射和神经元发育的基因。一些已鉴定的具有差异甲基化的基因(DLG 相关蛋白 2,雷帕霉素的机制靶点)先前已被认为与创伤应激有关。结果表明,经历过童年逆境的老年人出现了特定的表观遗传改变。精神和躯体合并症以及颊上皮细胞比例的差异可能导致观察到的表观遗传差异。本文的在线版本 (doi:10.1186/s12881-017-0370-2) 包含补充材料,可供授权用户使用。
Childhood trauma is associated with increased vulnerability to mental and somatic disorders later in life. Epigenetic modifications such as DNA methylation are one potential mechanism through which such long-lasting impairments/consequences can be explained. The aim of the present study was to investigate whether childhood trauma is associated with long-term DNA methylation alterations in old age. We assessed genome-wide DNA methylation profiles in a cohort of former indentured child laborers (“Verdingkinder”) who suffered severe childhood adversities (N = 30; M age = 75.9 years), and compared them to control group with similar demographic characteristics (N = 15, M age = 72.8 years). DNA was isolated from epithelial buccal cells and hybridized to the Illumina Infinium 450 k DNA methylation array, which provides coverage of 485,000 methylation sites. After accounting for batch effects, age, gender and multiple testing, 71 differentially methylated CpG positions were identified between the two groups. They were annotated among others to genes involved in neuronal projections and neuronal development. Some of the identified genes with differential methylation (DLG associated protein 2, mechanistic target of rapamycin) have previously been associated with traumatic stress. The results indicate specific epigenetic alterations in elderly individuals who were subjected to childhood adversities. Psychiatric and somatic comorbidities as well as differences in buccal epithelial cells proportion may contribute to the observed epigenetic differences. The online version of this article (doi:10.1186/s12881-017-0370-2) contains supplementary material, which is available to authorized users.