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. 2013 May;208(5):395.e1-7.
doi: 10.1016/j.ajog.2013.02.006. Epub 2013 Mar 8.

DNA methylation at imprint regulatory regions in preterm birth and infection

Ying Liu  1 , Cathrine Hoyo, Susan Murphy, Zhiqing Huang, Francine Overcash, Jennifer Thompson, Haywood Brown, Amy P Murtha
Affiliations

DNA methylation at imprint regulatory regions in preterm birth and infection

Ying Liu et al. Am J Obstet Gynecol. 2013 May.

Abstract

Objective: To aid in understanding long-term health consequences of intrauterine infections in preterm birth, we evaluated DNA methylation at 9 differentially methylated regions that regulate imprinted genes by type of preterm birth (spontaneous preterm labor, preterm premature rupture of membranes, or medically indicated [fetal growth restriction and preeclampsia]) and infection status (chorioamnionitis or funisitis).

Study design: Data on type of preterm birth and infection status were abstracted from medical records and standardized pathology reports in 73 preterm infants enrolled in the Newborn Epigenetics STudy, a prospective cohort study of mother-infant dyads in Durham, NC. Cord blood was collected at birth, and infant DNA methylation levels at the H19, IGF2, MEG3, MEST, SGCE/PEG10, PEG3, NNAT, and PLAGL1 differentially methylated regions were measured using bisulfite pyrosequencing. One-way analyses of variance and logistic regression models were used to compare DNA methylation levels by type of preterm birth and infection status.

Results: DNA methylation levels did not differ at any of the regions (P > .20) between infants born via spontaneous preterm labor (average n = 29), preterm premature rupture of membranes (average n = 17), or medically indicated preterm birth (average n = 40). Levels were significantly increased at PLAGL1 in infants with chorioamnionitis (n = 10, 64.4%) compared with infants without chorioamnionitis (n = 63, 57.9%), P < .01. DNA methylation levels were also increased at PLAGL1 for infants with funisitis (n = 7, 63.3%) compared with infants without funisitis (n = 66, 58.3%), P < .05.

Conclusion: Dysregulation of PLAGL1 has been associated with abnormal development and cancer. Early-life exposures, including infection/inflammation, may affect epigenetic changes that increase susceptibility to later chronic disease.

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Conflict of interest statement

Conflict of Interest: The authors report no conflicts of interest.

Figures

Figure 1
Figure 1
Distribution of DMRs by Type of PTB Summary: Median and IQR of infant DNA methylation levels at nine DMRs by type of PTB. There are no significant differences between mean methylation levels at any of the nine DMRs by type of PTB, p>0.20. (Reference line represents 50% methylation).
Figure 2
Figure 2
Infant DNA Methylation at PLAGL1 by Infection Summary: Median and IQR of infant DNA methylation levels at PLAGL1 by chorioamnionitis and funisitis. Mean DNA methylation levels at PLAGL1 are higher in infants who experienced chorioamnionitis (difference 6.5%, p=0.0026) and funisitis (difference 5.0%, p=0.0517) compared with infants who experienced no infection at birth.
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