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

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

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

dc.contributor.author	Hoyo, Cathrine
dc.contributor.author	Fortner, Kimberly
dc.contributor.author	Murtha, Amy P
dc.contributor.author	Schildkraut, Joellen M
dc.contributor.author	Soubry, Adelheid
dc.contributor.author	Demark-Wahnefried, Wendy
dc.contributor.author	Jirtle, Randy L
dc.contributor.author	Kurtzberg, Joanne
dc.contributor.author	Forman, Michele R
dc.contributor.author	Overcash, Francine
dc.contributor.author	Huang, Zhiqing
dc.contributor.author	Murphy, Susan K
dc.date.accessioned	2022-03-23T19:48:34Z
dc.date.available	2022-03-23T19:48:34Z
dc.date.issued	2012-04
dc.date.updated	2022-03-23T19:48:33Z
dc.description.abstract	Purpose 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. Methods 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. Results 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. Conclusion 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.
dc.identifier.issn	0957-5243
dc.identifier.issn	1573-7225
dc.identifier.uri	https://hdl.handle.net/10161/24671
dc.language	eng
dc.publisher	Springer Science and Business Media LLC
dc.relation.ispartof	Cancer causes & control : CCC
dc.relation.isversionof	10.1007/s10552-012-9932-y
dc.subject	Fetal Blood
dc.subject	Humans
dc.subject	Birth Weight
dc.subject	Insulin-Like Growth Factor II
dc.subject	Enzyme-Linked Immunosorbent Assay
dc.subject	DNA Methylation
dc.subject	Genomic Imprinting
dc.subject	Infant, Newborn
dc.subject	Female
dc.subject	Male
dc.title	Association of cord blood methylation fractions at imprinted insulin-like growth factor 2 (IGF2), plasma IGF2, and birth weight.
dc.type	Journal article
duke.contributor.orcid	Kurtzberg, Joanne\|0000-0002-3370-0703
duke.contributor.orcid	Murphy, Susan K\|0000-0001-8298-7272
pubs.begin-page	635
pubs.end-page	645
pubs.issue	4
pubs.organisational-group	Duke
pubs.organisational-group	Nicholas School of the Environment
pubs.organisational-group	School of Medicine
pubs.organisational-group	Faculty
pubs.organisational-group	Clinical Science Departments
pubs.organisational-group	Institutes and Centers
pubs.organisational-group	Family Medicine and Community Health
pubs.organisational-group	Pathology
pubs.organisational-group	Pediatrics
pubs.organisational-group	Family Medicine and Community Health, Prevention Research
pubs.organisational-group	Duke Cancer Institute
pubs.organisational-group	Environmental Sciences and Policy
pubs.organisational-group	Institutes and Provost's Academic Units
pubs.organisational-group	Initiatives
pubs.organisational-group	Duke Innovation & Entrepreneurship
pubs.organisational-group	Pediatrics, Transplant and Cellular Therapy
pubs.publication-status	Published
pubs.volume	23