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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Gestational Vitamin D Supplementation Leads to Reduced Perinatal RXRA DNA Methylation: Results From the MAVIDOS Trial
Journal of Bone and Mineral Research, Volume 34, No. 2, Year 2019
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Description
We have previously demonstrated inverse associations between maternal 25(OH)-vitamin D status and perinatal DNA methylation at the retinoid-X-receptor-alpha (RXRA) locus and between RXRA methylation and offspring bone mass. In this study, we used an existing randomized trial to test the hypothesis that maternal gestational vitamin D supplementation would lead to reduced perinatal RXRA locus DNA methylation. The Maternal Vitamin D Osteoporosis Study (MAVIDOS) was a multicenter, double-blind, randomized, placebo-controlled trial of 1000 IU/day cholecalciferol or matched placebo from 14 weeks’ gestation until delivery. Umbilical cord (fetal) tissue was collected at birth and frozen at −80°C (n = 453). Pyrosequencing was used to undertake DNA methylation analysis at 10 CpG sites within the RXRA locus (identified previously). T tests were used to assess differences between treatment groups in methylation at the three most representative CpG sites. Overall, methylation levels were significantly lower in the umbilical cord from offspring of cholecalciferol-supplemented mothers, reaching statistical significance at four CpG sites, represented by CpG5: mean difference in % methylation between the supplemented and placebo groups was −1.98% (95% CI, −3.65 to −0.32, p = 0.02). ENCODE (Encyclopedia of DNA Elements) evidence supports the functionality of this locus with strong DNase hypersensitivity and enhancer chromatin within biologically relevant cell types including osteoblasts. Enrichment of the enhancer-related H3K4me1 histone mark is also seen in this region, as are binding sites for a range of transcription factors with roles in cell proliferation, response to stress, and growth factors. Our findings are consistent with previous observational results and provide new evidence that maternal gestational supplementation with cholecalciferol leads to altered perinatal epigenetic marking, informing mechanistic understanding of early life mechanisms related to maternal vitamin D status, epigenetic marks, and bone development. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.
Authors & Co-Authors
Cook, Eloise
United Kingdom, Southampton
University of Southampton
D'Angelo, Stefania
United Kingdom, Southampton
Mrc Lifecourse Epidemiology Unit
Crozier, Sarah R.
United Kingdom, Southampton
Mrc Lifecourse Epidemiology Unit
Murray, Robert J.S.
United Kingdom, Southampton
University of Southampton
Garratt, Emma S.
United Kingdom, Southampton
University of Southampton
Costello, Paula M.
United Kingdom, Southampton
University of Southampton
Bishop, Nick J.
United Kingdom, Sheffield
Sheffield Children's Hospital
Kennedy, Stephen H.
United Kingdom, Oxford
John Radcliffe Hospital
Papageorghiou, Aris T.
United Kingdom, Oxford
John Radcliffe Hospital
Schoenmakers, Inez
United Kingdom, London
Medical Research Council
United Kingdom, Norwich
University of East Anglia
Fräser, Robert B.
United Kingdom, Wakefield
Nhs England
Prentice, Ann M.
United Kingdom, London
Medical Research Council
Javaid, Muhammad Kassim
United Kingdom, Oxford
Nihr Oxford Biomedical Research Centre
Inskip, Hazel M.
United Kingdom, Southampton
Mrc Lifecourse Epidemiology Unit
United Kingdom, Southampton
University of Southampton
Godfrey, Keith M.
United Kingdom, Southampton
Mrc Lifecourse Epidemiology Unit
United Kingdom, Southampton
University of Southampton
Lillycrop, Karen A.
United Kingdom, Southampton
University of Southampton
Cooper, Cyrus C.
United Kingdom, Southampton
Mrc Lifecourse Epidemiology Unit
United Kingdom, Oxford
Nihr Oxford Biomedical Research Centre
United Kingdom, Southampton
University of Southampton
Harvey, Nicholas C.W.
United Kingdom, Southampton
Mrc Lifecourse Epidemiology Unit
United Kingdom, Southampton
University of Southampton
Statistics
Citations: 30
Authors: 18
Affiliations: 9
Identifiers
Doi:
10.1002/jbmr.3603
ISSN:
08840431
Research Areas
Disability
Genetics And Genomics
Maternal And Child Health
Noncommunicable Diseases