Newborns of obese parents have altered DNA methylation patterns at imprinted genes.
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Several epidemiologic studies have demonstrated associations between periconceptional environmental exposures and health status of the offspring in later life. Although these environmentally related effects have been attributed to epigenetic changes, such as DNA methylation shifts at imprinted genes, little is known about the potential effects of maternal and paternal preconceptional overnutrition or obesity.We examined parental preconceptional obesity in relation to DNA methylation profiles at multiple human imprinted genes important in normal growth and development, such as: maternally expressed gene 3 (MEG3), mesoderm-specific transcript (MEST), paternally expressed gene 3 (PEG3), pleiomorphic adenoma gene-like 1 (PLAGL1), epsilon sarcoglycan and paternally expressed gene 10 (SGCE/PEG10) and neuronatin (NNAT).We measured methylation percentages at the differentially methylated regions (DMRs) by bisulfite pyrosequencing in DNA extracted from umbilical cord blood leukocytes of 92 newborns. Preconceptional obesity, defined as BMI ⩾30 kg m(-2), was ascertained through standardized questionnaires.After adjusting for potential confounders and cluster effects, paternal obesity was significantly associated with lower methylation levels at the MEST (β=-2.57; s.e.=0.95; P=0.008), PEG3 (β=-1.71; s.e.=0.61; P=0.005) and NNAT (β=-3.59; s.e.=1.76; P=0.04) DMRs. Changes related to maternal obesity detected at other loci were as follows: β-coefficient was +2.58 (s.e.=1.00; P=0.01) at the PLAGL1 DMR and -3.42 (s.e.=1.69; P=0.04) at the MEG3 DMR.We found altered methylation outcomes at multiple imprint regulatory regions in children born to obese parents, compared with children born to non-obese parents. In spite of the small sample size, our data suggest a preconceptional influence of parental life-style or overnutrition on the (re)programming of imprint marks during gametogenesis and early development. More specifically, the significant and independent association between paternal obesity and the offspring's methylation status suggests the susceptibility of the developing sperm for environmental insults. The acquired imprint instability may be carried onto the next generation and increase the risk for chronic diseases in adulthood.
Insulin-Like Growth Factor II
Cell Cycle Proteins
Tumor Suppressor Proteins
Nerve Tissue Proteins
Reproducibility of Results
Sequence Analysis, DNA
Kruppel-Like Transcription Factors
Published Version (Please cite this version)10.1038/ijo.2013.193
Publication InfoSoubry, A; Murphy, SK; Wang, F; Huang, Z; Vidal, AC; Fuemmeler, BF; ... Hoyo, C (2015). Newborns of obese parents have altered DNA methylation patterns at imprinted genes. International journal of obesity (2005), 39(4). pp. 650-657. 10.1038/ijo.2013.193. Retrieved from https://hdl.handle.net/10161/20701.
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Adjunct Associate Professor in the Department of Community and Family Medicine
Unhealthy lifestyle factors, such as tobacco use, poor dietary intake, lack of physical activity, and high body mass index are the leading causes of cancer and chronic disease. The prevention of such diseases will be advanced through a more thorough understanding of the complex determinants of these lifestyle factors and the development of novel interventions that help change individual behavior for the better. Dr. Fuemmeler’s program of research takes a lifespan approach toward understand
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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 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 transcripti
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
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
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
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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