Tyrka Audrey R, Parade Stephanie H, Eslinger Nicole M, Marsit Carmen J, Lesseur Corina, Armstrong David A, Philip Noah S, Josefson Brittney, Seifer Ronald
Butler Hospital.
Brown University Alpert Medical School.
Dev Psychopathol. 2015 May;27(2):577-85. doi: 10.1017/S0954579415000176.
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 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 6 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 1(D), 1(F), and 1(H) of the GR gene was measured via sodium bisulfite pyrosequencing. The composite measure of adversity was positively correlated with methylation at exons 1(D) and 1(F) in the promoter of the GR gene. Individual stress measures were significantly associated with a several CpG sites in these regions. GR gene methylation may be a mechanism of the biobehavioral effects of adverse exposures in young children.
基因组的表观遗传修饰是参与经验生物编码的关键机制。动物研究以及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个家庭参与了研究，其中74个家庭有过去6个月中中度至重度虐待的儿童福利记录。儿童年龄在3至5岁之间，种族和民族多样。通过结构化记录审查和在家中进行访谈来评估虐待史、其他创伤和背景生活压力源，一个综合变量评估了接触这些逆境的次数。通过亚硫酸氢盐焦磷酸测序法测量GR基因1（D）、1（F）和1（H）区域的甲基化。逆境的综合测量与GR基因启动子中外显子1（D）和1（F）的甲基化呈正相关。个体压力测量与这些区域的几个CpG位点显著相关。GR基因甲基化可能是幼儿不良暴露生物行为效应的一种机制。
