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. 2011 May;6(5):566-72.
doi: 10.4161/epi.6.5.15236. Epub 2011 May 1.

Birthweight is associated with DNA promoter methylation of the glucocorticoid receptor in human placenta

Amanda C Filiberto  1 , Matthew A Maccani, Devin Koestler, Charlotte Wilhelm-Benartzi, Michele Avissar-Whiting, Carolyn E Banister, Luc A Gagne, Carmen J Marsit
Affiliations

Birthweight is associated with DNA promoter methylation of the glucocorticoid receptor in human placenta

Amanda C Filiberto et al. Epigenetics. 2011 May.

Abstract

Birthweight has been associated with a number of health outcomes throughout life. Crucial to proper infant growth and development is the placenta, and alterations to placental gene function may reflect differences in the intrauterine environment which functionally contribute to infant growth and may ultimately affect the child's health. To examine if epigenetic alteration to the glucocorticoid receptor (GR) gene was linked to infant growth, we analyzed 480 human placentas for differential methylation of the GR gene exon 1F and examined how this variation in methylation extent was associated with fetal growth. Multivariable linear regression revealed a significant association (p < 0.0001) between differential methylation of the GR gene and large for gestational age (LGA) status. Our work is one of the first to link infant growth as a measure of the intrauterine environment and epigenetic alterations to the GR and suggests that DNA methylation may be a critical determinant of placental function.

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Figures

Figure 1
Figure 1
Comparison of the mean extent of methylation of the 13 CpG sites in the GR exon 1F promoter region in SGA (n = 102), AGA (n = 343) and LGA (n = 35) placentas determined by bisulfite pyrosequencing. Error bars represent standard error. * indicates p < 0.05 and ** indicates significant differential methylation following Bonferroni correction (p < 0.0036).
Figure 2
Figure 2
Correlation matrix describing pair wise Pearson correlations of methylation status among the 13 CpG sites within the exon 1F promoter region of the GR in all placenta samples (n = 480). Numbers in parentheses indicate bp distance of specific GR Position from GR Position 1.
Figure 3
Figure 3
Examination of the effects of 5-aza-2′deoxycytidine (5-azaC) on placenta choriocarcinoma cell line JEG-3. (A) Extent of methylation at CpG sites in GR exon 1F region examined by bisulfite pyrosequencing with increasing doses of 5-azaC. (B) Expression of GR mRNA examined by qRT-PCR with increasing doses of 5-azaC.
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