Erythrocyte folate concentrations, CpG methylation at genomically imprinted domains, and birth weight in a multiethnic newborn cohort.

Abstract

Epigenetic mechanisms are proposed to link maternal concentrations of methyl group donor nutrients with the risk of low birth weight. However, empirical data are lacking. We have examined the association between maternal folate and birth weight and assessed the mediating role of DNA methylation at nine differentially methylated regions (DMRs) of genomically imprinted genes in these associations. Compared with newborns of women with folate levels in the lowest quartile, birth weight was higher in newborns of mothers in the second (β = 143.2, se = 63.2, P = 0.02), third (β = 117.3, se = 64.0, P = 0.07), and fourth (β = 133.9, se = 65.2, P = 0.04) quartiles, consistent with a threshold effect. This pattern of association did not vary by race/ethnicity but was more apparent in newborns of non-obese women. DNA methylation at the PLAGL1, SGCE, DLK1/MEG3 and IGF2/H19 DMRs was associated with maternal folate levels and also birth weight, suggestive of threshold effects. MEG3 DMR methylation mediated the association between maternal folate levels and birth weight (P =0.06). While the small sample size and partial scope of examined DMRs limit our conclusions, our data suggest that, with respect to birth weight, no additional benefits may be derived from increased maternal folate concentrations, especially in non-obese women. These data also support epigenetic plasticity as a key mechanistic response to folate availability during early fetal development.

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Published Version (Please cite this version)

10.4161/epi.29332

Publication Info

Hoyo, Cathrine, Anne Kjersti Daltveit, Edwin Iversen, Sara E Benjamin-Neelon, Bernard Fuemmeler, Joellen Schildkraut, Amy P Murtha, Francine Overcash, et al. (2014). Erythrocyte folate concentrations, CpG methylation at genomically imprinted domains, and birth weight in a multiethnic newborn cohort. Epigenetics, 9(8). pp. 1120–1130. 10.4161/epi.29332 Retrieved from https://hdl.handle.net/10161/24655.

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Scholars@Duke

Iversen

Edwin Severin Iversen

Research Professor of Statistical Science

Bayesian statistical modeling with application to problems in genetic
epidemiology and cancer research; models for epidemiological risk
assessment, including hierarchical methods for combining related
epidemiological studies; ascertainment corrections for high risk
family data; analysis of high-throughput genomic data sets.

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.


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