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Epigenetic gene promoter methylation at birth is associated with childrens later adiposity

Epigenetic gene promoter methylation at birth is associated with childrens later adiposity
Epigenetic gene promoter methylation at birth is associated with childrens later adiposity
Objective: fixed genomic variation explains only a small proportion of the risk of adiposity. In animal models, maternal diet alters offspring body composition, accompanied by epigenetic changes in metabolic control genes. Little is known about whether such processes operate in humans.

Research design and methods: using Sequenom MassARRAY we measured the methylation status of 68 CpGs 5? from five candidate genes in umbilical cord tissue DNA from healthy neonates. Methylation varied greatly at particular CpGs: for 31 CpGs with median methylation ?5% and a 5–95% range ?10%, we related methylation status to maternal pregnancy diet and to child’s adiposity at age 9 years. Replication was sought in a second independent cohort.

Results: in cohort 1, retinoid X receptor-? (RXRA) chr9:136355885+ and endothelial nitric oxide synthase (eNOS) chr7:150315553+ methylation had independent associations with sex-adjusted childhood fat mass (exponentiated regression coefficient [?] 17% per SD change in methylation [95% CI 4–31], P = 0.009, n = 64, and ? = 20% [9–32], P < 0.001, n = 66, respectively) and %fat mass (? = 10% [1–19], P = 0.023, n = 64 and ? =12% [4–20], P = 0.002, n = 66, respectively). Regression analyses including sex and neonatal epigenetic marks explained >25% of the variance in childhood adiposity. Higher methylation of RXRA chr9:136355885+, but not of eNOS chr7:150315553+, was associated with lower maternal carbohydrate intake in early pregnancy, previously linked with higher neonatal adiposity in this population. In cohort 2, cord eNOS chr7:150315553+ methylation showed no association with adiposity, but RXRA chr9:136355885+ methylation showed similar associations with fat mass and %fat mass (? = 6% [2–10] and ? = 4% [1–7], respectively, both P = 0.002, n = 239).

Conclusions: our findings suggest a substantial component of metabolic disease risk has a prenatal developmental basis. Perinatal epigenetic analysis may have utility in identifying individual vulnerability to later obesity and metabolic disease
0012-1797
1528-1534
Godfrey, Keith M.
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Sheppard, Alan
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Gluckman, Peter D.
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Lillycrop, Karen A.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Burdge, Graham C.
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McClean, Cameron
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Rodford, Joanne
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Slater-Jefferies, Joanne L.
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Garratt, Emma
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Crozier, Sarah R.
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Emerald, B. Starling
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Gale, Catharine R.
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Inskip, Hazel M.
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Cooper, Cyrus
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Hanson, Mark A.
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Godfrey, Keith M.
0931701e-fe2c-44b5-8f0d-ec5c7477a6fd
Sheppard, Alan
c129c05a-7f5e-4d09-9f8a-b3917fed3399
Gluckman, Peter D.
ef2e8b92-0b76-4a12-bd7c-01b0674f94d3
Lillycrop, Karen A.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Burdge, Graham C.
09d60a07-8ca1-4351-9bf1-de6ffcfb2159
McClean, Cameron
aee26c86-40d6-4207-97bc-cf16d40b3ad5
Rodford, Joanne
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Slater-Jefferies, Joanne L.
e46c711a-9d4c-436a-b853-828df69bb4d7
Garratt, Emma
66ddd4cb-19a2-4d08-889b-12f418e6878b
Crozier, Sarah R.
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Emerald, B. Starling
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Gale, Catharine R.
5bb2abb3-7b53-42d6-8aa7-817e193140c8
Inskip, Hazel M.
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Cooper, Cyrus
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Hanson, Mark A.
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Godfrey, Keith M., Sheppard, Alan, Gluckman, Peter D., Lillycrop, Karen A., Burdge, Graham C., McClean, Cameron, Rodford, Joanne, Slater-Jefferies, Joanne L., Garratt, Emma, Crozier, Sarah R., Emerald, B. Starling, Gale, Catharine R., Inskip, Hazel M., Cooper, Cyrus and Hanson, Mark A. (2011) Epigenetic gene promoter methylation at birth is associated with childrens later adiposity. Diabetes, 60 (5), 1528-1534. (doi:10.2337/db10-0979). (PMID:21471513)

Record type: Article

Abstract

Objective: fixed genomic variation explains only a small proportion of the risk of adiposity. In animal models, maternal diet alters offspring body composition, accompanied by epigenetic changes in metabolic control genes. Little is known about whether such processes operate in humans.

Research design and methods: using Sequenom MassARRAY we measured the methylation status of 68 CpGs 5? from five candidate genes in umbilical cord tissue DNA from healthy neonates. Methylation varied greatly at particular CpGs: for 31 CpGs with median methylation ?5% and a 5–95% range ?10%, we related methylation status to maternal pregnancy diet and to child’s adiposity at age 9 years. Replication was sought in a second independent cohort.

Results: in cohort 1, retinoid X receptor-? (RXRA) chr9:136355885+ and endothelial nitric oxide synthase (eNOS) chr7:150315553+ methylation had independent associations with sex-adjusted childhood fat mass (exponentiated regression coefficient [?] 17% per SD change in methylation [95% CI 4–31], P = 0.009, n = 64, and ? = 20% [9–32], P < 0.001, n = 66, respectively) and %fat mass (? = 10% [1–19], P = 0.023, n = 64 and ? =12% [4–20], P = 0.002, n = 66, respectively). Regression analyses including sex and neonatal epigenetic marks explained >25% of the variance in childhood adiposity. Higher methylation of RXRA chr9:136355885+, but not of eNOS chr7:150315553+, was associated with lower maternal carbohydrate intake in early pregnancy, previously linked with higher neonatal adiposity in this population. In cohort 2, cord eNOS chr7:150315553+ methylation showed no association with adiposity, but RXRA chr9:136355885+ methylation showed similar associations with fat mass and %fat mass (? = 6% [2–10] and ? = 4% [1–7], respectively, both P = 0.002, n = 239).

Conclusions: our findings suggest a substantial component of metabolic disease risk has a prenatal developmental basis. Perinatal epigenetic analysis may have utility in identifying individual vulnerability to later obesity and metabolic disease

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More information

e-pub ahead of print date: 6 April 2011
Published date: May 2011
Organisations: Human Development & Health, Centre for Biological Sciences

Identifiers

Local EPrints ID: 337148
URI: http://eprints.soton.ac.uk/id/eprint/337148
ISSN: 0012-1797
PURE UUID: a35ba0af-5a90-470b-b1e7-aeb87df55947
ORCID for Keith M. Godfrey: ORCID iD orcid.org/0000-0002-4643-0618
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 Joanne L. Slater-Jefferies: ORCID iD orcid.org/0000-0001-8325-1320
ORCID for Emma Garratt: ORCID iD orcid.org/0000-0001-5268-4203
ORCID for Catharine R. Gale: ORCID iD orcid.org/0000-0002-3361-8638
ORCID for Hazel M. Inskip: ORCID iD orcid.org/0000-0001-8897-1749
ORCID for Cyrus Cooper: ORCID iD orcid.org/0000-0003-3510-0709
ORCID for Mark A. Hanson: ORCID iD orcid.org/0000-0002-6907-613X

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Date deposited: 19 Apr 2012 13:35
Last modified: 18 Mar 2024 03:03

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Contributors

Author: Alan Sheppard
Author: Peter D. Gluckman
Author: Cameron McClean
Author: Joanne Rodford
Author: Emma Garratt ORCID iD
Author: Sarah R. Crozier
Author: B. Starling Emerald
Author: Hazel M. Inskip ORCID iD
Author: Cyrus Cooper ORCID iD
Author: Mark A. Hanson ORCID iD

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