DNA methylation at imprint regulatory regions in preterm birth and infection

• Published in: American journal of obstetrics and gynecology 2013-05, Vol.208 (5), p.395.e1-395.e7
• Main Authors: Liu, Ying, MPH, Hoyo, Cathrine, PhD, Murphy, Susan, PhD, Huang, Zhiqing, MD, PhD, Overcash, Francine, MPH, Thompson, Jennifer, MD, Brown, Haywood, MD, Murtha, Amy P., MD
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Analysis of Variance; chorioamnionitis; Chorioamnionitis - genetics; Cross-Sectional Studies; DNA Methylation; epigenetic; Female; Fetal Blood; Fetal Membranes, Premature Rupture - genetics; funisitis; Genetic Markers; Genomic Imprinting; Humans; imprinting; Infant, Newborn; Labor, Induced; Logistic Models; Male; Obstetrics and Gynecology; Pregnancy; Premature Birth - etiology; Premature Birth - genetics; preterm birth; Prospective Studies; Sequence Analysis, DNA; Young Adult
• ISSN: 0002-9378; 1097-6868
• DOI: 10.1016/j.ajog.2013.02.006

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.