Methylation of exons 1D, 1F, and 1H of the glucocorticoid receptor gene promoter and exposure to adversity in preschool-aged children.
Methylation of exons 1D, 1F, and 1H of the glucocorticoid receptor gene promoter and exposure to adversity in preschool-aged children.
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DOI：
10.1017/s0954579415000176
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发表时间：
2015-05
影响因子：
3.3
通讯作者：
Seifer R
中科院分区：
文献类型：
--
作者：
Tyrka AR;Parade SH;Eslinger NM;Marsit CJ;Lesseur C;Armstrong DA;Philip NS;Josefson B;Seifer R
基因组的表观遗传修饰是参与经验生物编码的关键机制。动物研究和越来越多的人类文献表明，早期逆境与糖皮质激素受体（GR）基因的甲基化有关，GR是下丘脑-垂体-肾上腺（HPA）轴以及包括代谢和免疫功能在内的广泛生理系统的关键调节因子。184个家庭参加了研究，其中74个家庭在过去6个月内有中重度虐待的儿童福利记录。儿童年龄从3岁到5岁不等，种族和族裔各不相同。结构化的记录审查和访谈在家里被用来评估虐待的历史，其他创伤，和上下文的生活压力，和一个复合变量评估暴露于这些逆境的数量。通过亚硫酸氢钠焦磷酸测序测量GR基因的1D、1F和1H区的甲基化。逆境综合指标与NR 3C 1基因启动子1D和1F外显子甲基化呈正相关。个体应激指标与这些区域的几个CpG位点显著相关。GR基因甲基化可能是不良暴露对幼儿生物行为影响的机制之一。
Epigenetic modifications to the genome are a key mechanism involved in the biological encoding of experience. Animal studies and a growing body of literature in humans have shown that early adversity is linked to methylation of the gene for the glucocorticoid receptor (GR) which is a key regulator of the hypothalamic-pituitary-adrenal (HPA) axis as well as a broad range of physiological systems including metabolic and immune function. One hundred eighty-four families participated, including n=74 with child welfare documentation of moderate-severe maltreatment in the past six months. Children ranged in age from 3 to 5 years, and were racially and ethnically diverse. Structured record review and interviews in the home were used to assess a history of maltreatment, other traumas, and contextual life stressors, and a composite variable assessed the number exposures to these adversities. Methylation of regions 1D, 1F, and 1H of the GR gene was measured via sodium bisulfite pyrosequencing. The composite measure of adversity was positively correlated with methylation at exons 1D and 1F in the promoter of NR3C1. Individual stress measures were significantly associated with a several CpG sites in these regions. GR gene methylation may be a mechanism of the bio-behavioral effects of adverse exposures in young children.