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Association of cord blood methylation fractions at imprinted insulin-like growth factor 2 (IGF2), plasma IGF2, and birth weight.

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Date
2012-04
Authors
Hoyo, Cathrine
Fortner, Kimberly
Murtha, Amy P
Schildkraut, Joellen M
Soubry, Adelheid
Demark-Wahnefried, Wendy
Jirtle, Randy L
Kurtzberg, Joanne
Forman, Michele R
Overcash, Francine
Huang, Zhiqing
Murphy, Susan K
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Abstract
<h4>Purpose</h4>Altered methylation at Insulin-like Growth Factor 2 (IGF2) regulatory regions has previously been associated with obesity, and several malignancies including colon, esophageal, and prostate adenocarcinomas, presumably via changes in expression and/or loss of imprinting, but the functional significance of these DNA methylation marks have not been demonstrated in humans. We examined associations among DNA methylation at IGF2 differentially methylated regions (DMRs), circulating IGF2 protein concentrations in umbilical cord blood (UCB) and birth weight in newborns.<h4>Methods</h4>Questionnaire data were obtained from 300 pregnant women recruited between 2005 and 2009. UCB DNA methylation was measured by bisulfite pyrosequencing. UCB plasma concentrations of soluble IGF2 were measured by ELISA assays. Generalized linear regression models were used to examine the relationship between DMR methylation and IGF2 levels.<h4>Results</h4>Lower IGF2 DMR methylation was associated with elevated plasma IGF2 protein concentrations (β = -9.87, p < 0.01); an association that was stronger in infants born to obese women (pre-pregnancy BMI > 30 kg/m(2), β = -20.21, p < 0.0001). Elevated IGF2 concentrations were associated with higher birth weight (p < 0.0001) after adjusting for maternal race/ethnicity, pre-pregnancy BMI, cigarette smoking, gestational diabetes, and infant sex. These patterns of association were not apparent at the H19 DMR.<h4>Conclusion</h4>Our data suggest that variation in IGF2 DMR methylation is an important mechanism by which circulating IGF2 concentrations, a putative risk factor for obesity and cancers of the colon, esophagus, and prostate, are modulated; associations that may depend on pre-pregnancy obesity.
Type
Journal article
Subject
Fetal Blood
Humans
Birth Weight
Insulin-Like Growth Factor II
Enzyme-Linked Immunosorbent Assay
DNA Methylation
Genomic Imprinting
Infant, Newborn
Female
Male
Permalink
https://hdl.handle.net/10161/24671
Published Version (Please cite this version)
10.1007/s10552-012-9932-y
Publication Info
Hoyo, Cathrine; Fortner, Kimberly; Murtha, Amy P; Schildkraut, Joellen M; Soubry, Adelheid; Demark-Wahnefried, Wendy; ... Murphy, Susan K (2012). Association of cord blood methylation fractions at imprinted insulin-like growth factor 2 (IGF2), plasma IGF2, and birth weight. Cancer causes & control : CCC, 23(4). pp. 635-645. 10.1007/s10552-012-9932-y. Retrieved from https://hdl.handle.net/10161/24671.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Huang

Zhiqing Huang

Assistant Professor in Obstetrics and Gynecology
Dr. Huang is an Assistant Professor in the Department of Obstetrics and Gynecology, Division of Reproductive Sciences, at Duke University Medical Center. She obtained her MD at North China Coal Medical University in China and her PhD at the University of Heidelberg in Germany under the mentorship of Dr. Ralph Witzgall. She did her postdoctoral training with Dr. Jiemin Wong at Baylor College of Medicine, studying how histone methylation and chromatin modifications regulate androgen receptor tr
Kurtzberg

Joanne Kurtzberg

Jerome S. Harris Distinguished Professor of Pediatrics
Dr. Kurtzberg conducts both clinical and laboratory-based translational research efforts, all involving various aspects of normal and malignant hematopoiesis. In the laboratory, her early work focused on studies determining the mechanisms that regulate the choice between the various pathways of differentiation available to the pluripotent hematopoietic stem cell. Her laboratory established a CD7+ cell line, DU.528, capable of multilineage differentiation as well as self-renewal, and subse
Murphy

Susan Kay Murphy

Associate Professor in Obstetrics and Gynecology
My research interests are largely centered around epigenetics and the role of epigenetic modifications in health and disease. My research projects include studies of gynecologic malignancies, including working on approaches to target ovarian cancer cells that survive chemotherapy and later give rise to recurrent disease.  I have ongoing collaborative projects in which we investigate the nature of the Developmental Origins of Health and Disease (DOHaD) hypothesis. DOHaD reflects the ide
Murtha

Amy Patricia Murtha

Professor of Obstetrics and Gynecology
Dr. Amy Murtha is a Professor in the Department of Obstetrics and Gynecology and Department of Pediatrics, and past Vice Chair for Research in Obstetrics and Gynecology. After graduating from the Medical College of Pennsylvania in 1992 she completed her residency in OB-GYN and fellowship in Maternal Fetal Medicine (MFM) at Duke University then joined the faculty at Duke in 1998.  Dr. Murtha served as interim Chair for the Department of OB-GYN and Fellowship Director for the mater
Schildkraut

Joellen Martha Schildkraut

Professor Emeritus in Family Medicine and Community Health
Dr. Schildkraut is an epidemiologist whose research includes the molecular epidemiology of ovarian, breast and brain cancers. Dr. Schildkraut's research interests include the study of the interaction between genetic and environmental factors. She is currently involved in a large study of genome wide association and ovarian cancer risk and survival. Some of her work is also focused on particular genetic pathways including the DNA repair and apoptosis pathways. She currently leads a study of
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