DNA methylation profiling at imprinted loci after periconceptional micronutrient supplementation in humans

Results of a pilot randomized controlled trial

Wendy N. Cooper, Khulan Batbayar, Stephen Owens, Cathy E. Elks, Veronica Seidel, Andrew M. Prentice, Gusztav Belteki, Ken K. Ong, Nabeel A. Affara, Miguel Constância, David B. Dunger

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

Intrauterine exposures mediated by maternal diet may affect risk of cardiovascular disease, obesity, and type 2 diabetes. Recent evidence, primarily from animal studies and observational data in humans, suggests that the epigenome can be altered by maternal diet during the periconceptional period and that these programming events may underlie later disease risk. A randomized controlled trial of periconceptional micronutrient supplementation in The Gambia, where seasonal nutritional variations affect fetal growth and postnatal outcomes, provided a unique opportunity to test this hypothesis. Specifically, we targeted imprinted genes, which play important roles in allocation of maternal resources while being epigenetically regulated. DNA methylation at 12 differentially methylated regions (DMRs) was analyzed in cord blood samples from 58 offspring of women participating in a doubleblind randomized-controlled trial of pre- and periconceptional micronutrient supplementation (including folate, zinc, and vitamins A, B, C, and D). We observed sex-specific effects of micronutrient supplementation, reducing methylation levels at two of the DMRs analyzed, IGF2R in girls and GTL2-2 in boys. This pilot study is the first to analyze DNA methylation in the context of a randomized controlled trial, and it provides suggestive evidence that periconceptional maternal nutrition alters offspring methylation at imprinted loci.

Original languageEnglish (US)
Pages (from-to)1782-1790
Number of pages9
JournalFASEB Journal
Volume26
Issue number5
DOIs
StatePublished - May 1 2012
Externally publishedYes

Fingerprint

DNA Fingerprinting
Micronutrients
DNA Methylation
Nutrition
Methylation
Randomized Controlled Trials
Mothers
Gambia
Diet
Maternal Exposure
Resource Allocation
Medical problems
Fetal Development
Vitamin A
Fetal Blood
Folic Acid
Type 2 Diabetes Mellitus
Observational Studies
Zinc
Animals

Keywords

  • Epigenetics
  • Fetal programming
  • Maternal nutrition

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

DNA methylation profiling at imprinted loci after periconceptional micronutrient supplementation in humans : Results of a pilot randomized controlled trial. / Cooper, Wendy N.; Batbayar, Khulan; Owens, Stephen; Elks, Cathy E.; Seidel, Veronica; Prentice, Andrew M.; Belteki, Gusztav; Ong, Ken K.; Affara, Nabeel A.; Constância, Miguel; Dunger, David B.

In: FASEB Journal, Vol. 26, No. 5, 01.05.2012, p. 1782-1790.

Research output: Contribution to journalArticle

Cooper, WN, Batbayar, K, Owens, S, Elks, CE, Seidel, V, Prentice, AM, Belteki, G, Ong, KK, Affara, NA, Constância, M & Dunger, DB 2012, 'DNA methylation profiling at imprinted loci after periconceptional micronutrient supplementation in humans: Results of a pilot randomized controlled trial', FASEB Journal, vol. 26, no. 5, pp. 1782-1790. https://doi.org/10.1096/fj.11-192708
Cooper, Wendy N. ; Batbayar, Khulan ; Owens, Stephen ; Elks, Cathy E. ; Seidel, Veronica ; Prentice, Andrew M. ; Belteki, Gusztav ; Ong, Ken K. ; Affara, Nabeel A. ; Constância, Miguel ; Dunger, David B. / DNA methylation profiling at imprinted loci after periconceptional micronutrient supplementation in humans : Results of a pilot randomized controlled trial. In: FASEB Journal. 2012 ; Vol. 26, No. 5. pp. 1782-1790.
@article{fd83a1b646df45e3bdb06da56c185025,
title = "DNA methylation profiling at imprinted loci after periconceptional micronutrient supplementation in humans: Results of a pilot randomized controlled trial",
abstract = "Intrauterine exposures mediated by maternal diet may affect risk of cardiovascular disease, obesity, and type 2 diabetes. Recent evidence, primarily from animal studies and observational data in humans, suggests that the epigenome can be altered by maternal diet during the periconceptional period and that these programming events may underlie later disease risk. A randomized controlled trial of periconceptional micronutrient supplementation in The Gambia, where seasonal nutritional variations affect fetal growth and postnatal outcomes, provided a unique opportunity to test this hypothesis. Specifically, we targeted imprinted genes, which play important roles in allocation of maternal resources while being epigenetically regulated. DNA methylation at 12 differentially methylated regions (DMRs) was analyzed in cord blood samples from 58 offspring of women participating in a doubleblind randomized-controlled trial of pre- and periconceptional micronutrient supplementation (including folate, zinc, and vitamins A, B, C, and D). We observed sex-specific effects of micronutrient supplementation, reducing methylation levels at two of the DMRs analyzed, IGF2R in girls and GTL2-2 in boys. This pilot study is the first to analyze DNA methylation in the context of a randomized controlled trial, and it provides suggestive evidence that periconceptional maternal nutrition alters offspring methylation at imprinted loci.",
keywords = "Epigenetics, Fetal programming, Maternal nutrition",
author = "Cooper, {Wendy N.} and Khulan Batbayar and Stephen Owens and Elks, {Cathy E.} and Veronica Seidel and Prentice, {Andrew M.} and Gusztav Belteki and Ong, {Ken K.} and Affara, {Nabeel A.} and Miguel Const{\^a}ncia and Dunger, {David B.}",
year = "2012",
month = "5",
day = "1",
doi = "10.1096/fj.11-192708",
language = "English (US)",
volume = "26",
pages = "1782--1790",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "5",

}

TY - JOUR

T1 - DNA methylation profiling at imprinted loci after periconceptional micronutrient supplementation in humans

T2 - Results of a pilot randomized controlled trial

AU - Cooper, Wendy N.

AU - Batbayar, Khulan

AU - Owens, Stephen

AU - Elks, Cathy E.

AU - Seidel, Veronica

AU - Prentice, Andrew M.

AU - Belteki, Gusztav

AU - Ong, Ken K.

AU - Affara, Nabeel A.

AU - Constância, Miguel

AU - Dunger, David B.

PY - 2012/5/1

Y1 - 2012/5/1

N2 - Intrauterine exposures mediated by maternal diet may affect risk of cardiovascular disease, obesity, and type 2 diabetes. Recent evidence, primarily from animal studies and observational data in humans, suggests that the epigenome can be altered by maternal diet during the periconceptional period and that these programming events may underlie later disease risk. A randomized controlled trial of periconceptional micronutrient supplementation in The Gambia, where seasonal nutritional variations affect fetal growth and postnatal outcomes, provided a unique opportunity to test this hypothesis. Specifically, we targeted imprinted genes, which play important roles in allocation of maternal resources while being epigenetically regulated. DNA methylation at 12 differentially methylated regions (DMRs) was analyzed in cord blood samples from 58 offspring of women participating in a doubleblind randomized-controlled trial of pre- and periconceptional micronutrient supplementation (including folate, zinc, and vitamins A, B, C, and D). We observed sex-specific effects of micronutrient supplementation, reducing methylation levels at two of the DMRs analyzed, IGF2R in girls and GTL2-2 in boys. This pilot study is the first to analyze DNA methylation in the context of a randomized controlled trial, and it provides suggestive evidence that periconceptional maternal nutrition alters offspring methylation at imprinted loci.

AB - Intrauterine exposures mediated by maternal diet may affect risk of cardiovascular disease, obesity, and type 2 diabetes. Recent evidence, primarily from animal studies and observational data in humans, suggests that the epigenome can be altered by maternal diet during the periconceptional period and that these programming events may underlie later disease risk. A randomized controlled trial of periconceptional micronutrient supplementation in The Gambia, where seasonal nutritional variations affect fetal growth and postnatal outcomes, provided a unique opportunity to test this hypothesis. Specifically, we targeted imprinted genes, which play important roles in allocation of maternal resources while being epigenetically regulated. DNA methylation at 12 differentially methylated regions (DMRs) was analyzed in cord blood samples from 58 offspring of women participating in a doubleblind randomized-controlled trial of pre- and periconceptional micronutrient supplementation (including folate, zinc, and vitamins A, B, C, and D). We observed sex-specific effects of micronutrient supplementation, reducing methylation levels at two of the DMRs analyzed, IGF2R in girls and GTL2-2 in boys. This pilot study is the first to analyze DNA methylation in the context of a randomized controlled trial, and it provides suggestive evidence that periconceptional maternal nutrition alters offspring methylation at imprinted loci.

KW - Epigenetics

KW - Fetal programming

KW - Maternal nutrition

UR - http://www.scopus.com/inward/record.url?scp=84860909449&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84860909449&partnerID=8YFLogxK

U2 - 10.1096/fj.11-192708

DO - 10.1096/fj.11-192708

M3 - Article

VL - 26

SP - 1782

EP - 1790

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 5

ER -