Association of cord blood methylation fractions at imprinted insulin-like growth factor 2 (IGF2), plasma IGF2, and birth weight.
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 articleSubject
Fetal BloodHumans
Birth Weight
Insulin-Like Growth Factor II
Enzyme-Linked Immunosorbent Assay
DNA Methylation
Genomic Imprinting
Infant, Newborn
Female
Male
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https://hdl.handle.net/10161/24671Published Version (Please cite this version)
10.1007/s10552-012-9932-yPublication 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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Show full item recordScholars@Duke
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
Joanne Kurtzberg
Jerome S. Harris Distinguished Professor of Pediatrics
Dr. Kurtzberg is an internationally renowned expert in pediatric hematology/oncology,
pediatric blood and marrow transplantation, umbilical cord blood banking and transplantation,
and novel applications of cord blood and birthing tissues in the emerging fields of
cellular therapies and regenerative medicine. Dr. Kurtzberg serves as the Director
of the Marcus Center for Cellular Cures (MC3), Director of the Pediatric Transplant
and Cellular Therapy Program, Director of the Carolina
Susan Kay Murphy
Associate Professor in Obstetrics and Gynecology
Dr. Murphy is a tenured Associate Professor in the Department of Obstetrics and Gynecology
and serves as Chief of the Division of Reproductive Sciences. As a molecular biologist
with training in human epigenetics, her research interests are largely centered around
the role of epigenetic modifications in health and disease. Dr. Murphy has ongoing
projects on gynecologic malignancies, including approaches to eradicate ovarian cancer
cells that survive chemotherapy and later give r
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
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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