Maternal B vitamins: effects on offspring weight and DNA methylation at genomically imprinted domains.

Abstract

BACKGROUND:

Inadequate maternal nutrition during early fetal development can create permanent alterations in the offspring, leading to poor health outcomes. While nutrients involved in one-carbon cycle metabolism are important to fetal growth, associations with specific nutrients remain inconsistent. This study estimates associations between maternal vitamins B12, B6 (pyridoxal phosphate [PLP] and 4-pyridoxic acid [PA]), and homocysteine (Hcy) concentrations, offspring weight (birth weight and 3-year weight gain), and DNA methylation at four differentially methylated regions (DMRs) known to be involved in fetal growth and development (H19, MEG3, SGCE/PEG10, and PLAGL1).

METHODS:

Study participants (n = 496) with biomarker and birth weight data were enrolled as part of the Newborn Epigenetics STudy. Weight gain data were available for 273 offspring. Among 484 mother-infant pairs, DNA methylation at regulatory sequences of genomically imprinted genes was measured in umbilical cord blood DNA using bisulfite pyrosequencing. We used generalized linear models to estimate associations.

RESULTS:

Multivariate adjusted regression models revealed an inverse association between maternal Hcy concentration and male birth weight (β = -210.40, standard error (SE) = 102.08, p = 0.04). The offspring of the mothers in the highest quartile of B12 experienced lower weight gain between birth and 3 years compared to the offspring of the mothers in the lowest (β = -2203.03, SE = 722.49, p = 0.003). Conversely, maternal PLP was associated with higher weight gain in males; higher maternal PLP concentrations were also associated with offspring DNA methylation levels at the MEG3 DMR (p < 0.01).

CONCLUSIONS:

While maternal concentrations of B12, B6, and Hcy do not associate with birth weight overall, they may play an important role in 3-year weight gain. This is the first study to report an association between maternal PLP and methylation at the MEG3 DMR which may be an important epigenetic tag for maternal B vitamin adequacy.

• Authors: Lauren E McCullough, Erline E Miller, Michelle A Mendez, Amy P Murtha, Susan K Murphy, Cathrine Hoyo
• Journal: Clinical epigenetics (Clin Epigenetics) Vol. 8 Pg. 8 ( 2016) ISSN: 1868-7075 [Print] Germany
• PMID: 26807160 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Cell Cycle Proteins
• H19 long non-coding RNA
• MEG3 non-coding RNA, human
• PLAGL1 protein, human
• RNA, Long Noncoding
• SGCE protein, human
• Sarcoglycans
• Transcription Factors
• Tumor Suppressor Proteins
• Homocysteine
• Vitamin B 6
• Vitamin B 12

Topics

• Adult
• Birth Weight (genetics, physiology)
• Cell Cycle Proteins (genetics)
• Child, Preschool
• DNA Methylation (physiology)
• Female
• Homocysteine (blood)
• Humans
• Infant, Newborn
• Male
• Pregnancy (blood)
• RNA, Long Noncoding (genetics)
• Sarcoglycans (genetics)
• Transcription Factors (genetics)
• Tumor Suppressor Proteins (genetics)
• Vitamin B 12 (blood)
• Vitamin B 6 (blood)
• Weight Gain (genetics, physiology)
• Young Adult