Insulin-like growth factor 2/H19 methylation at birth and risk of overweight and obesity in children.

Abstract

Objective

To determine whether aberrant DNA methylation at differentially methylated regions (DMRs) regulating insulin-like growth factor 2 (IGF2) expression in umbilical cord blood is associated with overweight or obesity in a multiethnic cohort.

Study design

Umbilical cord blood leukocytes of 204 infants born between 2005 and 2009 in Durham, North Carolina, were analyzed for DNA methylation at two IGF2 DMRs by using pyrosequencing. Anthropometric and feeding data were collected at age 1 year. Methylation differences were compared between children >85th percentile of the Centers for Disease Control and Prevention growth charts weight-for-age (WFA) and children ≤ 85th percentile of WFA at 1 year by using generalized linear models, adjusting for post-natal caloric intake, maternal cigarette smoking, and race/ethnicity.

Results

The methylation percentages at the H19 imprint center DMR was higher in infants with WFA >85th percentile (62.7%; 95% CI, 59.9%-65.5%) than in infants with WFA ≤ 85th percentile (59.3%; 95% CI, 58.2%-60.3%; P = .02). At the intragenic IGF2 DMR, methylation levels were comparable between infants with WFA ≤ 85th percentile and infants with WFA >85th percentile.

Conclusions

Our findings suggest that IGF2 plasticity may be mechanistically important in early childhood overweight or obese status. If confirmed in larger studies, these findings suggest aberrant DNA methylation at sequences regulating imprinted genes may be useful identifiers of children at risk for the development of early obesity.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1016/j.jpeds.2012.01.015

Publication Info

Perkins, Ellen, Susan K Murphy, Amy P Murtha, Joellen Schildkraut, Randy L Jirtle, Wendy Demark-Wahnefried, Michele R Forman, Joanne Kurtzberg, et al. (2012). Insulin-like growth factor 2/H19 methylation at birth and risk of overweight and obesity in children. The Journal of pediatrics, 161(1). pp. 31–39. 10.1016/j.jpeds.2012.01.015 Retrieved from https://hdl.handle.net/10161/24681.

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.

Scholars@Duke

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 African American women diagnosed with ovarian cancer. She is also collaborating in a large a case-control study of meningioma risk factors and with which a genome wide association analysis is about to commence.

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 transcription. 

Dr. Huang’s research includes the following:

•The factors in the tumor microenvironment contribute to ovarian cancer progress;
•New drug development for recurrent ovarian cancer treatment;
•The early DNA methylation profiles contribute to cancer development in late life;
•The special changes in the tumor microenvironment;
•Epigenetics and epigenomics.
*The impact of lipid metabolism in the tumor microenvironment in cancer progression and treatment.
*Impact of ferroptosis in endometriosis development. 

Dr. Huang has received an R03 funding titled “Role of Age-Related Changes in the Tumor Microenvironment on Ovarian Cancer Progression” from NIA at NIH for 2021-2023.
Dr. Huang received Charles B. Hammond's Research Fund from the Department of Obstetrics and Gynecology at Duke University in November 2022, for a project titled "Single Cell Spatial Transcriptomics in Highly Aggressive and Less Aggressive Ovarian Cancer".
Dr. Huang has received Duke Cancer Institute 2023 spring pilot study award for07012023-06302024, the project title is "Age Effects on Chemotherapy Targeting Cells Causing Ovarian Cancer Recurrence”.
Dr. Huang has received the American Cancer Society -Duke Cancer Institute (ASC-DCI) 2024 spring pilot study award for 07012024-06302025. The project title is "Early Establishment of Epigenetic Profiles that Increase Cancer Risk in Late Life”.
Dr. Huang received Charles B. Hammond's Research Fund from the Department of Obstetrics and Gynecology at Duke University in November 2023 for 01012024-12312024. The project's title is "Age Effects on Chemotherapy Targeting Cells Causing Ovarian Cancer Recurrence".


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