Research Article

Genetic and epigenetic variation of the glucocorticoid receptor (NR3C1) in placenta and infant neurobehavior†

  1. Cailey Bromer1,
  2. Carmen J. Marsit2,3,
  3. David A. Armstrong3,
  4. James F. Padbury2,4,
  5. Barry Lester1,2,4

Article first published online: 19 JUN 2012

DOI: 10.1002/dev.21061

Additional Information

How to Cite

Bromer, C., Marsit, C. J., Armstrong, D. A., Padbury, J. F. and Lester, B. (2012), Genetic and epigenetic variation of the glucocorticoid receptor (NR3C1) in placenta and infant neurobehavior. Dev. Psychobiol.. doi: 10.1002/dev.21061

Author Information

  1. 1

    The Brown Center for the Study of Children at Risk, Women & Infants Hospital of Rhode Island, Providence, RI 02903

  2. 2

    Department of Pediatrics, Women & Infants Hospital of Rhode Island, Providence, RI 02903

  3. 3

    Departments of Pharmacology and Toxicology and Community and Family Medicine Section Epidemiology and Biostatistics, Dartmouth Medical School, Hanover, NH 03755

  4. 4

    Brown Alpert Medical School, Providence, RI 02903

  1. †

    The authors have no conflicts of interest to declare.

Publication History

  1. Article first published online: 19 JUN 2012
  2. Manuscript Accepted: 26 MAY 2012
  3. Manuscript Received: 16 NOV 2011

Funded by

  • NCRR. Grant Number: P20 RR018728
  • NIMH. Grant Number: R01 MH094609

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Keywords:

  • epigenetic;
  • glucocorticoid receptor;
  • placenta;
  • neurodevelopment;
  • human;
  • attention;
  • quality of movement

Abstract

The intrauterine environment can impact the developing infant by altering the function of the placenta through changes to the epigenetic regulatory features of this tissue. Genetic variation, too, may impact infant development or may modify the relationship between epigenetic alterations and infant outcomes. To examine the associations of these variations with early life infant neurodevelopment, we examined the extent of DNA methylation of the glucocorticoid receptor gene (NR3C1) promoter and a common single nucleotide polymorphism in the promoter region in a series of 186 placentas from healthy newborn infants. We associated these molecular features with specific summary measures from the NICU Network Neurobehavioral Scales. After controlling for genotype and confounders, we identified significant associations of NR3C1 methylation with infant quality of movement (p = .05) and with infant attention (p = .05), and a potential interaction between methylation and genotype on infant attention score. These results suggest that epigenetic alteration of the NR3C1 gene in the placentas of genetically susceptible infants can have impacts on neurodevelopment which may have lifelong impact on neurobehavioral and mental health outcomes. Further research is needed to more precisely define these relationships and the interaction between epigenetic alterations and genetic variations on infant health. © 2012 Wiley Periodicals, Inc. Dev Psychobiol

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