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Folate and vitamin B12 status: associations with maternal glucose and neonatal DNA methylation sites related to dysglycaemia, in pregnant women with obesity

Folate and vitamin B12 status: associations with maternal glucose and neonatal DNA methylation sites related to dysglycaemia, in pregnant women with obesity
Folate and vitamin B12 status: associations with maternal glucose and neonatal DNA methylation sites related to dysglycaemia, in pregnant women with obesity

Recent studies implicate maternal gestational diabetes mellitus (GDM) in differential methylation of infant DNA. Folate and vitamin B12 play a role in DNA methylation, and these vitamins may also influence GDM risk. The aims of this study were to determine folate and vitamin B12 status in obese pregnant women and investigate associations between folate and vitamin B12 status, maternal dysglycaemia and neonatal DNA methylation at cytosine-phosphate-guanine sites previously observed to be associated with dysglycaemia. Obese pregnant women who participated in the UK Pregnancies Better Eating and Activity Trial were included. Serum folate and vitamin B12 were measured at the oral glucose tolerance test (OGTT) visit. Cord blood DNA methylation was assessed using the Infinium MethylationEPIC BeadChip. Regression models with adjustment for confounders were used to examine associations. Of the 951 women included, 356 (37.4%) were vitamin B12 deficient, and 44 (4.6%) were folate deficient. Two-hundred and seventy-one women (28%) developed GDM. Folate and vitamin B12 concentrations were not associated with neonatal DNA methylation. Higher folate was positively associated with 1-h plasma glucose after OGTT (β = 0.031, 95% CI 0.001-0.061, p = 0.045). There was no relationship between vitamin B12 and glucose concentrations post OGTT or between folate or vitamin B12 and GDM. In summary, we found no evidence to link folate and vitamin B12 status with the differential methylation of neonatal DNA previously observed in association with dysglycaemia. We add to the evidence that folate status may be related to maternal glucose homoeostasis although replication in other maternal cohorts is required for validation.

DNA methylation, Folate, gestational diabetes mellitus, maternal obesity, vitamin B12
168-176
Weelden, Wenneke van
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Seed, Paul T.
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Antoun, Elie
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Godfrey, Keith
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Kitaba, Negusse
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Lillycrop, Karen
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Dalrymple, Kathryn V.
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Sobczyńska-Malefora, Agata
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Painter, Rebecca C.
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Poston, Lucilla
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White, Sara L.
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Flynn, Angela
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Weelden, Wenneke van
fbd90fd3-b2c5-4ac6-9fb0-c84eae8ee870
Seed, Paul T.
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Antoun, Elie
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Godfrey, Keith
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Kitaba, Negusse
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Lillycrop, Karen
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Dalrymple, Kathryn V.
8ef94198-4e90-44a9-b77d-19d35d013cde
Sobczyńska-Malefora, Agata
8887e6df-c8e4-4b94-8788-a9645c421627
Painter, Rebecca C.
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Poston, Lucilla
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White, Sara L.
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Flynn, Angela
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Weelden, Wenneke van, Seed, Paul T., Antoun, Elie, Godfrey, Keith, Kitaba, Negusse, Lillycrop, Karen, Dalrymple, Kathryn V., Sobczyńska-Malefora, Agata, Painter, Rebecca C., Poston, Lucilla, White, Sara L. and Flynn, Angela (2021) Folate and vitamin B12 status: associations with maternal glucose and neonatal DNA methylation sites related to dysglycaemia, in pregnant women with obesity. Journal of Developmental Origins of Health and Disease, 13 (2), 168-176. (doi:10.1017/S2040174421000246).

Record type: Article

Abstract

Recent studies implicate maternal gestational diabetes mellitus (GDM) in differential methylation of infant DNA. Folate and vitamin B12 play a role in DNA methylation, and these vitamins may also influence GDM risk. The aims of this study were to determine folate and vitamin B12 status in obese pregnant women and investigate associations between folate and vitamin B12 status, maternal dysglycaemia and neonatal DNA methylation at cytosine-phosphate-guanine sites previously observed to be associated with dysglycaemia. Obese pregnant women who participated in the UK Pregnancies Better Eating and Activity Trial were included. Serum folate and vitamin B12 were measured at the oral glucose tolerance test (OGTT) visit. Cord blood DNA methylation was assessed using the Infinium MethylationEPIC BeadChip. Regression models with adjustment for confounders were used to examine associations. Of the 951 women included, 356 (37.4%) were vitamin B12 deficient, and 44 (4.6%) were folate deficient. Two-hundred and seventy-one women (28%) developed GDM. Folate and vitamin B12 concentrations were not associated with neonatal DNA methylation. Higher folate was positively associated with 1-h plasma glucose after OGTT (β = 0.031, 95% CI 0.001-0.061, p = 0.045). There was no relationship between vitamin B12 and glucose concentrations post OGTT or between folate or vitamin B12 and GDM. In summary, we found no evidence to link folate and vitamin B12 status with the differential methylation of neonatal DNA previously observed in association with dysglycaemia. We add to the evidence that folate status may be related to maternal glucose homoeostasis although replication in other maternal cohorts is required for validation.

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W van Weelden et al. Manuscript text tables and figures - clean version - Accepted Manuscript
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Accepted/In Press date: 6 April 2021
e-pub ahead of print date: 11 May 2021
Published date: 11 May 2021
Additional Information: Funding Information: We thank the Pedigree and Population Resource of Huntsman Cancer Institute, University of Utah (funded in part by the Huntsman Cancer Foundation) for its role in the ongoing collection, maintenance and support of the Utah Population Database (UPDB). We also acknowledge partial support for the UPDB through grant P30 CA2014 from the National Cancer Institute , University of Utah and from the University of Utah 's program in Personalized Health and Center for Clinical and Translational Science . Publisher Copyright: © The Author(s), 2021. Published by Cambridge University Press in association with International Society for Developmental Origins of Health and Disease.
Keywords: DNA methylation, Folate, gestational diabetes mellitus, maternal obesity, vitamin B12

Identifiers

Local EPrints ID: 448411
URI: http://eprints.soton.ac.uk/id/eprint/448411
PURE UUID: 45d844dd-8cc9-442a-92aa-f9b6c2f61319
ORCID for Keith Godfrey: ORCID iD orcid.org/0000-0002-4643-0618
ORCID for Negusse Kitaba: ORCID iD orcid.org/0000-0001-7518-9096
ORCID for Karen Lillycrop: ORCID iD orcid.org/0000-0001-7350-5489

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Date deposited: 21 Apr 2021 16:35
Last modified: 17 Mar 2024 06:29

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Contributors

Author: Wenneke van Weelden
Author: Paul T. Seed
Author: Elie Antoun
Author: Keith Godfrey ORCID iD
Author: Negusse Kitaba ORCID iD
Author: Karen Lillycrop ORCID iD
Author: Kathryn V. Dalrymple
Author: Agata Sobczyńska-Malefora
Author: Rebecca C. Painter
Author: Lucilla Poston
Author: Sara L. White
Author: Angela Flynn

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