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Methylation of exons 1D, 1F, and 1H of the glucocorticoid receptor gene promoter and exposure to adversity in preschool-aged children

  • Audrey R. Tyrka (a1) (a2), Stephanie H. Parade (a2) (a3), Nicole M. Eslinger (a1), Carmen J. Marsit (a4), Corina Lesseur (a4), David A. Armstrong (a4), Noah S. Philip (a1) (a2), Brittney Josefson (a3) and Ronald Seifer (a2) (a3)...

Abstract

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 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 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.

Copyright

Corresponding author

Address correspondence and reprint requests to: Audrey R. Tyrka, Butler Hospital, 345 Blackstone Boulevard, Providence, RI 02906; E-mail: Audrey_Tyrka@brown.edu.

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Methylation of exons 1D, 1F, and 1H of the glucocorticoid receptor gene promoter and exposure to adversity in preschool-aged children

  • Audrey R. Tyrka (a1) (a2), Stephanie H. Parade (a2) (a3), Nicole M. Eslinger (a1), Carmen J. Marsit (a4), Corina Lesseur (a4), David A. Armstrong (a4), Noah S. Philip (a1) (a2), Brittney Josefson (a3) and Ronald Seifer (a2) (a3)...

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