title: Maternal blood lead concentrations, DNA methylation ofMEG3DMR regulating the DLK1/MEG3 imprinted domain and early growth in a multiethnic cohort.
abstract: Prenatal exposure to lead (Pb) is known to decrease fetal growth; but its effects on postnatal growth and mechanistic insights linking Pb to growth are not clearly defined. Genomically imprinted genes are powerful regulators of growth and energy utilization, and may be particularly vulnerable to environmental Pb exposure. Because imprinting is established early and maintained via DNA methylation, we hypothesized that prenatal Pb exposure alters DNA methylation of imprinted genes resulting in lower birth weight and rapid growth. Pb was measured by inductively coupled plasma mass spectrometry (ICP-MS) in peripheral blood of 321 women of the Newborn Epigenetic STudy (NEST) obtained at gestation ~12 weeks. Linear and logistic regression models were used to evaluate associations between maternal Pb levels, methylation of differentially methylated regions (DMRs) regulatingH19, MEG3,PEG3,andPLAGL1,measured by pyrosequencing, birth weight, and weight-for-height z score gains between birth and age 1yr, ages 1-2yrs, and 2-3yrs. Children born to women with Pb levels in the upper tertile had higher methylation of the regulatory region of theMEG3DMR imprinted domain (β= 1.57, se= 0.82, p= 0.06). Pb levels were also associated with lower birth weight (β= -0.41, se= 0.15, p= 0.01) and rapid gains in adiposity (OR= 12.32, 95%CI=1.25-121.30, p= 0.03) by age 2-3 years. These data provide early human evidence for Pb associations with hypermethylation at theMEG3DMR regulatory region and rapid adiposity gain-a risk factor for childhood obesity and cardiometabolic diseases in adulthood.
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke University, B226 LSRC, Box 91012, Research Drive, Durham, NC 27708, USA; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, 450 West Street, CB 7295, UNC, Chapel Hill, NC 27599, USA; Department of Environmental Sciences and Engineering, Curriculum in Toxicology, The University of North Carolina at Chapel Hill, 135 Dauer Drive, CB 7431, UNC, Chapel Hill, NC 27599.
authors.forename: Monica D
authors.initials: MD
authors.lastname: Nye
authors.affiliation: Environmental Public Health Division, U.S. Environmental Protection Agency and Department of Community and Family Medicine, Duke University, Durham, NC, USA.
authors.forename: Katherine E
authors.initials: KE
authors.lastname: King
authors.affiliation: School of Earth Sciences, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Darrah
authors.affiliation: Department of Biological Sciences, Center for Human Health and Environment, Campus Box 7633, NC State University, Raleigh, NC 27695, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Maguire
authors.affiliation: Department of Biological Sciences, Center for Human Health and Environment, Campus Box 7633, NC State University, Raleigh, NC 27695, USA.
authors.forename: Dereje D
authors.initials: DD
authors.lastname: Jima
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke University, B226 LSRC, Box 91012, Research Drive, Durham, NC 27708, USA.
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, 450 West Street, CB 7295, UNC, Chapel Hill, NC 27599, USA; Department of Nutrition, Gillings School of Public Health Fellow, Carolina Population Center University of North Carolina at Chapel Hill; 2101G McGavran-Greenberg Hall Chapel Hill, NC 27599-7461.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Mendez
authors.affiliation: Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, 450 West Street, CB 7295, UNC, Chapel Hill, NC 27599, USA; Department of Environmental Sciences and Engineering, Curriculum in Toxicology, The University of North Carolina at Chapel Hill, 135 Dauer Drive, CB 7431, UNC, Chapel Hill, NC 27599.
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Fry
authors.affiliation: Department of Biological Sciences, Center for Human Health and Environment, Campus Box 7633, NC State University, Raleigh, NC 27695, USA.
authors.forename: Randy L
authors.initials: RL
authors.lastname: Jirtle
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke University, B226 LSRC, Box 91012, Research Drive, Durham, NC 27708, USA.
authors.forename: Susan K
authors.initials: SK
authors.lastname: Murphy
authors.affiliation: Department of Biological Sciences, Center for Human Health and Environment, Campus Box 7633, NC State University, Raleigh, NC 27695, USA.
authors.forename: Cathrine
authors.initials: C
authors.lastname: Hoyo
keywords: DNA methylation; Environmental exposures; Epigenetics; Lead; MEG3