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Childhood bone mineral content is associated with methylation status of the RXRA promoter at birth

Childhood bone mineral content is associated with methylation status of the RXRA promoter at birth
Childhood bone mineral content is associated with methylation status of the RXRA promoter at birth
Maternal vitamin D deficiency has been associated with reduced offspring bone mineral accrual. Retinoid-X Receptor-alpha (RXRA) is an essential cofactor in the action of 1,25(OH)2-vitamin D, and RXRA methylation in umbilical cord DNA has been associated with later offspring adiposity. We tested the hypothesis that RXRA methylation in umbilical cord DNA collected at birth is associated with offspring skeletal development, assessed by dual-energy X-ray absorptiometry, in a population-based mother-offspring cohort (Southampton Women's Survey). Relationships between maternal plasma 25(OH)-vitamin D concentrations and cord RXRA methylation were also investigated. In 230 children aged 4 years, higher % methylation at 4 out of 6 RXRA CpG sites measured was correlated with lower offspring BMC corrected for body size (??=???2.1 to ?3.4g/SD, p?=?0.002 to 0.047). In a second independent cohort (n?=?64), similar negative associations at two of these CpG sites, but positive associations at the two remaining sites, were observed; however none of the relationships in this replication cohort achieved statistical significance. Maternal free 25(OH)-vitamin D index was negatively associated with methylation at one of these RXRA CpG sites (??=???3.3 SD/unit, p?=?0.03). Thus, perinatal epigenetic marking at the RXRA promoter region in umbilical cord was inversely associated with offspring size-corrected bone mineral content in childhood. The potential mechanistic and functional significance of this finding remains a subject for further investigation.
epigenetic, methylation, umbilical cord, rxra, vitamin D, dxa
0884-0431
Harvey, N.C.
ce487fb4-d360-4aac-9d17-9466d6cba145
Sheppard, A.
016f7049-e466-43c8-a299-a9f7a7d2542f
Godfrey, K.M.
0931701e-fe2c-44b5-8f0d-ec5c7477a6fd
McLean, C.
edab5d33-f937-44b1-b376-14cd369b56b7
Garratt, Emma
66ddd4cb-19a2-4d08-889b-12f418e6878b
Ntani, G.
9b009e0a-5ab2-4c6e-a9fd-15a601e92be5
DAVIES, LUCY
a45d8083-28ec-4d43-9037-616fd5cddb07
Murray, Robert
c3e973b5-525c-49b3-96ee-af60a666a0f4
Inskip, H.M.
5fb4470a-9379-49b2-a533-9da8e61058b7
Gluckman, P.D.
492295c0-ef71-4871-ad5a-771c98e1059a
Hanson, Mark
1952fad1-abc7-4284-a0bc-a7eb31f70a3f
Lillycrop, K.A.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Cooper, C.
e05f5612-b493-4273-9b71-9e0ce32bdad6
Harvey, N.C.
ce487fb4-d360-4aac-9d17-9466d6cba145
Sheppard, A.
016f7049-e466-43c8-a299-a9f7a7d2542f
Godfrey, K.M.
0931701e-fe2c-44b5-8f0d-ec5c7477a6fd
McLean, C.
edab5d33-f937-44b1-b376-14cd369b56b7
Garratt, Emma
66ddd4cb-19a2-4d08-889b-12f418e6878b
Ntani, G.
9b009e0a-5ab2-4c6e-a9fd-15a601e92be5
DAVIES, LUCY
a45d8083-28ec-4d43-9037-616fd5cddb07
Murray, Robert
c3e973b5-525c-49b3-96ee-af60a666a0f4
Inskip, H.M.
5fb4470a-9379-49b2-a533-9da8e61058b7
Gluckman, P.D.
492295c0-ef71-4871-ad5a-771c98e1059a
Hanson, Mark
1952fad1-abc7-4284-a0bc-a7eb31f70a3f
Lillycrop, K.A.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Cooper, C.
e05f5612-b493-4273-9b71-9e0ce32bdad6

Harvey, N.C., Sheppard, A., Godfrey, K.M., McLean, C., Garratt, Emma, Ntani, G., DAVIES, LUCY, Murray, Robert, Inskip, H.M., Gluckman, P.D., Hanson, Mark, Lillycrop, K.A. and Cooper, C. (2013) Childhood bone mineral content is associated with methylation status of the RXRA promoter at birth. Journal of Bone and Mineral Research. (doi:10.1002/jbmr.2056). (PMID:23907847)

Record type: Article

Abstract

Maternal vitamin D deficiency has been associated with reduced offspring bone mineral accrual. Retinoid-X Receptor-alpha (RXRA) is an essential cofactor in the action of 1,25(OH)2-vitamin D, and RXRA methylation in umbilical cord DNA has been associated with later offspring adiposity. We tested the hypothesis that RXRA methylation in umbilical cord DNA collected at birth is associated with offspring skeletal development, assessed by dual-energy X-ray absorptiometry, in a population-based mother-offspring cohort (Southampton Women's Survey). Relationships between maternal plasma 25(OH)-vitamin D concentrations and cord RXRA methylation were also investigated. In 230 children aged 4 years, higher % methylation at 4 out of 6 RXRA CpG sites measured was correlated with lower offspring BMC corrected for body size (??=???2.1 to ?3.4g/SD, p?=?0.002 to 0.047). In a second independent cohort (n?=?64), similar negative associations at two of these CpG sites, but positive associations at the two remaining sites, were observed; however none of the relationships in this replication cohort achieved statistical significance. Maternal free 25(OH)-vitamin D index was negatively associated with methylation at one of these RXRA CpG sites (??=???3.3 SD/unit, p?=?0.03). Thus, perinatal epigenetic marking at the RXRA promoter region in umbilical cord was inversely associated with offspring size-corrected bone mineral content in childhood. The potential mechanistic and functional significance of this finding remains a subject for further investigation.

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More information

Published date: 1 August 2013
Keywords: epigenetic, methylation, umbilical cord, rxra, vitamin D, dxa
Organisations: Epidemiology, Human Development & Health

Identifiers

Local EPrints ID: 359495
URI: http://eprints.soton.ac.uk/id/eprint/359495
ISSN: 0884-0431
PURE UUID: 931f5dd0-87a6-4058-b34e-7f83fe5a1cea
ORCID for N.C. Harvey: ORCID iD orcid.org/0000-0002-8194-2512
ORCID for K.M. Godfrey: ORCID iD orcid.org/0000-0002-4643-0618
ORCID for Emma Garratt: ORCID iD orcid.org/0000-0001-5268-4203
ORCID for H.M. Inskip: ORCID iD orcid.org/0000-0001-8897-1749
ORCID for Mark Hanson: ORCID iD orcid.org/0000-0002-6907-613X
ORCID for K.A. Lillycrop: ORCID iD orcid.org/0000-0001-7350-5489
ORCID for C. Cooper: ORCID iD orcid.org/0000-0003-3510-0709

Catalogue record

Date deposited: 04 Nov 2013 11:13
Last modified: 28 Apr 2022 01:52

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Contributors

Author: N.C. Harvey ORCID iD
Author: A. Sheppard
Author: K.M. Godfrey ORCID iD
Author: C. McLean
Author: Emma Garratt ORCID iD
Author: G. Ntani
Author: LUCY DAVIES
Author: Robert Murray
Author: H.M. Inskip ORCID iD
Author: P.D. Gluckman
Author: Mark Hanson ORCID iD
Author: K.A. Lillycrop ORCID iD
Author: C. Cooper ORCID iD

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