Adverse childhood experiences such as maltreatment or neglect are associated with mental health problems in adulthood. Changes in the regulation of the psychological and physiological stress reaction, mediated via epigenetic modifications, are discussed as potential mechanisms. This study aimed to replicate the role of DNA methylation of the KITLG gene in mediating the association between childhood adversity and stress-induced cortisol reactivity in a sample of adults reporting childhood adversity and a matched control group (N = 60). DNA was extracted from purified CD14+ monocytes and genome-wide DNA methylation was assessed with the 450k BeadChip for targeted replication and exploratory analyses. As previously reported, childhood adversity was associated with significantly lower cortisol reactivity to stress. We could neither replicate the association between KITLG DNA methylation and cortisol stress reactivity nor the association with childhood adversity. Moreover, DNA methylation of the target CpG (cg27512205) was not associated with KITLG mRNA expression in monocytes. Exploratory analyses of array-wide DNA methylation patterns showed no significant results for individual sites after correction for multiple testing - neither in association with childhood trauma nor with adult cortisol stress reactivity. The analysis of differentially methylated regions (DMRs) revealed two significant regions which both mapped to non-coding genes in the association with cortisol stress reactivity. The mediating role of DNA methylation of the KITLG locus in the association between childhood adversity and cortisol stress reactivity could not be replicated in monocytes. In addition to differences in investigated tissue, reasons for non-replication might include differences between samples in age, ethnicity, trauma severity, and cortisol reactivity.

中文翻译：

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KITLG DNA甲基化在童年逆境与皮质醇应激反应之间的中介作用在单核细胞中不复制

童年时期的不良经历，如虐待或忽视，与成年期的心理健康问题有关。通过表观遗传修饰介导的心理和生理应激反应调节的变化被讨论为潜在的机制。本研究旨在在报告童年逆境的成年人样本和匹配的对照组（N = 60）中复制 KITLG 基因的 DNA 甲基化在介导童年逆境与压力诱导的皮质醇反应性之间关联中的作用。从纯化的 CD14+ 单核细胞中提取 DNA，并使用 450k BeadChip 评估全基因组 DNA 甲基化，以进行靶向复制和探索性分析。正如之前报道的那样，童年逆境与对压力的皮质醇反应显着降低有关。我们既无法复制 KITLG DNA 甲基化与皮质醇应激反应之间的关联，也无法复制与童年逆境的关联。此外，目标 CpG (cg27512205) 的 DNA 甲基化与单核细胞中的 KITLG mRNA 表达无关。对全阵列 DNA 甲基化模式的探索性分析显示，经过多次测试校正后，单个位点没有显着结果——既与儿童期创伤无关，也与成人皮质醇应激反应无关。差异甲基化区域 (DMR) 的分析揭示了两个重要区域，它们都映射到与皮质醇应激反应相关的非编码基因。KITLG 基因座的 DNA 甲基化在童年逆境与皮质醇应激反应之间的关联中的介导作用无法在单核细胞中复制。