Department of Pediatrics, Howard University, Washington, D.C., United States of America.
Department of Microbiology & The National Human Genome Center, Howard University, Washington, D.C., United States of America.
PLoS One. 2022 Sep 6;17(9):e0273717. doi: 10.1371/journal.pone.0273717. eCollection 2022.
Low socioeconomic status neighborhood exposure to stress and violence may be sources of negative stimuli that poses significant health risks for children, adolescents and throughout the life course of an individual. The study aims to investigate if aberrant epigenetic DNA methylation changes may be a potential mechanism for regulating neighborhood exposures and health outcomes.
Exposure to environmental stressors identified in 98 young African American (AA) adults aged 18-25 years old from the Washington D.C., area were used in the study. We correlated the association between stress markers; cortisol, CRP, IgG, IGA, IgM, and self-reported exposure to violence and stress, with quantitative DNA methylation changes in a panel of gene-specific loci using saliva DNA.
In all participants studied, the exposure to violence was significant and negatively correlated with DNA methylation of MST1R loci (p = 0.032; r = -0.971) and nominally significant with NR3C1 loci (p = 0.053; r = -0.948). In addition, we observed significant and negative correlation of DNA methylation changes of LINE1 (p = 0.044; r = -0.248); NR3C1 (p = 0.017; r = -0.186); MSTR1 (p = 0.022; r = -0.192); and DRD2 (p = 0.056; r = -0.184; albeit nominal significant correlation) with IgA expression. On the other hand, we observed a significant and position correlation of DNA methylation changes in DRD2 (p = 0.037; r = 0.184) with IgG expression. When participants were stratified by sex, we observed in AA young male adults, significant DNA methylation changes of MST1R (p< 0.05) and association with exposure to violence and IgG level. We also observed significant DNA methylation levels of DRD2 (p< 0.05) and association with IgA, IgG, and cortisol level. Furthermore, we observed significant DNA methylation changes of NR3C1 (p< 0.05) with stress, IgA, and IgG in the male participants only. On the other hand, we only observed significant and a positive association of IgG with DNA methylation levels of ESR1 (p = 0.041) in the young AA female participants.
Our preliminary observation of significant DNA methylation changes in neuronal and immune genes in saliva samples supports our recently published genome-wide DNA methylations changes in blood samples from young AA male adults indicating that saliva offers a non-invasive means for DNA methylation prediction of exposure to environmental stressors in a gender-specific manner.
处于低社会经济地位的社区面临的压力和暴力可能是对儿童、青少年和个体整个生命过程造成重大健康风险的负面刺激源。本研究旨在探讨异常的表观遗传 DNA 甲基化变化是否可能是调节社区暴露和健康结果的潜在机制。
研究中使用了来自华盛顿特区的 98 名年龄在 18-25 岁之间的年轻非裔美国人（AA）的环境应激源暴露数据。我们将应激标志物（皮质醇、CRP、IgG、IgA、IgM）与自我报告的暴力和应激暴露相关联，同时使用唾液 DNA 检测一组基因特异性基因座的定量 DNA 甲基化变化。
在所有研究参与者中，暴力暴露与 MST1R 基因座的 DNA 甲基化呈显著负相关（p = 0.032；r = -0.971），与 NR3C1 基因座的 DNA 甲基化呈显著负相关（p = 0.053；r = -0.948）。此外，我们观察到 LINE1（p = 0.044；r = -0.248）、NR3C1（p = 0.017；r = -0.186）、MSTR1（p = 0.022；r = -0.192）和 DRD2（p = 0.056；r = -0.184；尽管是名义上的显著相关性）的 DNA 甲基化变化与 IgA 表达呈显著负相关。另一方面，我们观察到 DRD2 基因座的 DNA 甲基化变化与 IgG 表达呈显著的位置相关（p = 0.037；r = 0.184）。当按性别对参与者进行分层时，我们在 AA 年轻男性中观察到 MST1R 的 DNA 甲基化变化（p < 0.05），并与暴力暴露和 IgG 水平相关。我们还观察到 DRD2 基因座的 DNA 甲基化水平显著变化（p < 0.05），与 IgA、IgG 和皮质醇水平相关。此外，我们还观察到 NR3C1 基因座的 DNA 甲基化变化与应激、IgA 和 IgG 在男性参与者中具有显著相关性（p < 0.05）。另一方面，我们仅观察到 IgG 与 ESR1 基因座的 DNA 甲基化水平呈显著正相关（p = 0.041），这与我们最近发表的年轻 AA 男性血液样本中的全基因组 DNA 甲基化变化一致，表明唾液可提供一种非侵入性的方法，以性别特异性的方式预测环境应激源的暴露。
