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Evaluation of methylation status of the eNOS promoter at birth in relation to childhood bone mineral content

Evaluation of methylation status of the eNOS promoter at birth in relation to childhood bone mineral content
Evaluation of methylation status of the eNOS promoter at birth in relation to childhood bone mineral content
Our previous work has shown associations between childhood adiposity and perinatal methylation status of several genes in umbilical cord tissue, including endothelial nitric oxide synthase (eNOS). There is increasing evidence that eNOS is important in bone metabolism; we therefore related the methylation status of the eNOS gene promoter in stored umbilical cord to childhood bone size and density in a group of 9-year-old children. We used Sequenom MassARRAY to assess the methylation status of two CpGs in the eNOS promoter, identified from our previous study, in stored umbilical cords of 66 children who formed part of a Southampton birth cohort and who had measurements of bone size and density at age 9 years (Lunar DPXL DXA instrument). Percentage methylation varied greatly between subjects. For one of the two CpGs, eNOS chr7:150315553 + , after taking account of age and sex, there were strong positive associations between methylation status and the child’s whole-body bone area (r = 0.28, P = 0.02), bone mineral content (r = 0.34, P = 0.005), and areal bone mineral density (r = 0.34, P = 0.005) at age 9 years. These associations were independent of previously documented maternal determinants of offspring bone mass. Our findings suggest an association between methylation status at birth of a specific CpG within the eNOS promoter and bone mineral content in childhood. This supports a role for eNOS in bone growth and metabolism and implies that its contribution may at least in part occur during early skeletal development.
epigenesis, methylation, umbilical cord, eNOS, DXA
0171-967X
120-127
Harvey, Nicholas C.
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Lillycrop, Karen A.
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Garratt, Emma
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Sheppard, Allan
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McLean, Cameron
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Burdge, Graham C.
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Slater-Jefferies, Jo
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Rodford, Joanne
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Crozier, Sarah
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Inskip, Hazel
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Emerald, B.S.
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Gale, C.R.
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Hanson, M.
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Gluckman, P.
dadc86d4-4eaa-4589-b560-413a9e564558
Godfrey, K.
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Cooper, C.
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Harvey, Nicholas C.
ce487fb4-d360-4aac-9d17-9466d6cba145
Lillycrop, Karen A.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Garratt, Emma
863257ac-3150-4e33-b0ae-1d9d4e8c6614
Sheppard, Allan
a6e27895-05ad-4b0b-98bb-4aa033b7182d
McLean, Cameron
245194c5-ff48-4da4-9e5f-c437dc67dae4
Burdge, Graham C.
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Slater-Jefferies, Jo
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Rodford, Joanne
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Crozier, Sarah
a9c88016-8f46-4659-954e-4d7af8a49594
Inskip, Hazel
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Emerald, B.S.
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Gale, C.R.
5bb2abb3-7b53-42d6-8aa7-817e193140c8
Hanson, M.
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Gluckman, P.
dadc86d4-4eaa-4589-b560-413a9e564558
Godfrey, K.
0931701e-fe2c-44b5-8f0d-ec5c7477a6fd
Cooper, C.
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Harvey, Nicholas C., Lillycrop, Karen A., Garratt, Emma, Sheppard, Allan, McLean, Cameron, Burdge, Graham C., Slater-Jefferies, Jo, Rodford, Joanne, Crozier, Sarah, Inskip, Hazel, Emerald, B.S., Gale, C.R., Hanson, M., Gluckman, P., Godfrey, K. and Cooper, C. (2012) Evaluation of methylation status of the eNOS promoter at birth in relation to childhood bone mineral content. Calcified Tissue International, 90 (2), 120-127. (doi:10.1007/s00223-011-9554-5). (PMID:22159788)

Record type: Article

Abstract

Our previous work has shown associations between childhood adiposity and perinatal methylation status of several genes in umbilical cord tissue, including endothelial nitric oxide synthase (eNOS). There is increasing evidence that eNOS is important in bone metabolism; we therefore related the methylation status of the eNOS gene promoter in stored umbilical cord to childhood bone size and density in a group of 9-year-old children. We used Sequenom MassARRAY to assess the methylation status of two CpGs in the eNOS promoter, identified from our previous study, in stored umbilical cords of 66 children who formed part of a Southampton birth cohort and who had measurements of bone size and density at age 9 years (Lunar DPXL DXA instrument). Percentage methylation varied greatly between subjects. For one of the two CpGs, eNOS chr7:150315553 + , after taking account of age and sex, there were strong positive associations between methylation status and the child’s whole-body bone area (r = 0.28, P = 0.02), bone mineral content (r = 0.34, P = 0.005), and areal bone mineral density (r = 0.34, P = 0.005) at age 9 years. These associations were independent of previously documented maternal determinants of offspring bone mass. Our findings suggest an association between methylation status at birth of a specific CpG within the eNOS promoter and bone mineral content in childhood. This supports a role for eNOS in bone growth and metabolism and implies that its contribution may at least in part occur during early skeletal development.

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More information

e-pub ahead of print date: 8 December 2011
Published date: February 2012
Keywords: epigenesis, methylation, umbilical cord, eNOS, DXA
Organisations: Faculty of Medicine, Human Development & Health, Centre for Biological Sciences

Identifiers

Local EPrints ID: 336532
URI: http://eprints.soton.ac.uk/id/eprint/336532
ISSN: 0171-967X
PURE UUID: 5d4d33c8-8f00-4bb6-bb54-ffd370c86739
ORCID for Nicholas C. Harvey: ORCID iD orcid.org/0000-0002-8194-2512
ORCID for Karen A. Lillycrop: ORCID iD orcid.org/0000-0001-7350-5489
ORCID for Graham C. Burdge: ORCID iD orcid.org/0000-0002-7665-2967
ORCID for Jo Slater-Jefferies: ORCID iD orcid.org/0000-0001-8325-1320
ORCID for Hazel Inskip: ORCID iD orcid.org/0000-0001-8897-1749
ORCID for C.R. Gale: ORCID iD orcid.org/0000-0002-3361-8638
ORCID for M. Hanson: ORCID iD orcid.org/0000-0002-6907-613X
ORCID for K. Godfrey: ORCID iD orcid.org/0000-0002-4643-0618
ORCID for C. Cooper: ORCID iD orcid.org/0000-0003-3510-0709

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Date deposited: 30 Mar 2012 15:09
Last modified: 18 Mar 2024 03:03

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Contributors

Author: Emma Garratt
Author: Allan Sheppard
Author: Cameron McLean
Author: Joanne Rodford
Author: Sarah Crozier
Author: Hazel Inskip ORCID iD
Author: B.S. Emerald
Author: C.R. Gale ORCID iD
Author: M. Hanson ORCID iD
Author: P. Gluckman
Author: K. Godfrey ORCID iD
Author: C. Cooper ORCID iD

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