Dynamic changes in DNA methylation occur during the first Year of life in preterm infants

Chinthika Piyasena, Jessy Cartier, Nadine Provença, Tobias Wiechmann, Khulan Batbayar, Raju Sunderasan, Gopi Menon, Jonathan R. Seckl, Rebecca M. Reynolds, Elisabeth B. Binder, Amanda J. Drake

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Preterm birth associates with a substantially increased risk of later cardiovascular disease and neurodevelopmental disorders. Understanding underlying mechanisms will facilitate the development of screening and intervention strategies to reduce disease risk. Changes in DNA methylation have been proposed as one mechanism linking the early environment with later disease risk. We tested the hypothesis that preterm birth associates with altered DNA methylation in genes encoding insulin-like growth factor 2 (IGF2) and FK506-binding protein 5 (FKBP5), which appear particularly vulnerable to early life adversity. Methods: Fifty preterm infants were seen and assessed at birth, term equivalent age, 3 months and 1-year corrected ages; 40 term infants were seen at birth, 3 months and 1 year. Saliva was collected for DNA extraction at birth, term, and 1 year. Pyrosequencing of bisulfite-converted DNA was performed to measure DNA methylation at specific CpG sites within the IGF2 and FKBP5 loci. Results: Weight and head circumference was reduced in preterm infants at all time points. Preterm infants had a higher percentage body fat at term-corrected age, but this difference was not persistent. DNA methylation at the differentially methylated region (DMR) of IGF2 (IGF2DMR2) and FKBP5 was lower in preterm infants at birth- and term-corrected age compared to term infants at birth. IGF2DMR2 and FKBP5 methylation was related to birthweight SD score in preterm infants. Among preterm infants, social deprivation was an independent contributor toward reducing DNA methylation at IGFlDMR2 at birth- and term-corrected age and maternal smoking was associated with reduced DNA methylation at FKBP5 at birth. There were no persistent differences in DNA methylation at 1 year of age. Conclusion: Changes in DNA methylation were identified at key regions of IGF2/H19 and FKBP5 in preterm infants in early life. Potential contributing factors include maternal smoking and social deprivation. However, these changes did not persist at 1 year of age and further longitudinal studies are required to determine any associations between altered DNA methylation in the perinatal period of individuals born preterm and their long-term health.

Original languageEnglish (US)
Article number158
JournalFrontiers in Endocrinology
Volume7
Issue numberDEC
DOIs
StatePublished - Jan 1 2016
Externally publishedYes

Fingerprint

DNA Methylation
Premature Infants
Parturition
Somatomedins
Premature Birth
Smoking
DNA
Maternal Age
Saliva
Methylation
Longitudinal Studies
tacrolimus binding protein 5
Adipose Tissue
Cardiovascular Diseases
Head
Mothers
Weights and Measures
Health

Keywords

  • DNA methylation
  • FKBP5
  • Glucocorticoids
  • IGF2
  • Prematurity

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

Cite this

Piyasena, C., Cartier, J., Provença, N., Wiechmann, T., Batbayar, K., Sunderasan, R., ... Drake, A. J. (2016). Dynamic changes in DNA methylation occur during the first Year of life in preterm infants. Frontiers in Endocrinology, 7(DEC), [158]. https://doi.org/10.3389/fendo.2016.00158

Dynamic changes in DNA methylation occur during the first Year of life in preterm infants. / Piyasena, Chinthika; Cartier, Jessy; Provença, Nadine; Wiechmann, Tobias; Batbayar, Khulan; Sunderasan, Raju; Menon, Gopi; Seckl, Jonathan R.; Reynolds, Rebecca M.; Binder, Elisabeth B.; Drake, Amanda J.

In: Frontiers in Endocrinology, Vol. 7, No. DEC, 158, 01.01.2016.

Research output: Contribution to journalArticle

Piyasena, C, Cartier, J, Provença, N, Wiechmann, T, Batbayar, K, Sunderasan, R, Menon, G, Seckl, JR, Reynolds, RM, Binder, EB & Drake, AJ 2016, 'Dynamic changes in DNA methylation occur during the first Year of life in preterm infants', Frontiers in Endocrinology, vol. 7, no. DEC, 158. https://doi.org/10.3389/fendo.2016.00158
Piyasena, Chinthika ; Cartier, Jessy ; Provença, Nadine ; Wiechmann, Tobias ; Batbayar, Khulan ; Sunderasan, Raju ; Menon, Gopi ; Seckl, Jonathan R. ; Reynolds, Rebecca M. ; Binder, Elisabeth B. ; Drake, Amanda J. / Dynamic changes in DNA methylation occur during the first Year of life in preterm infants. In: Frontiers in Endocrinology. 2016 ; Vol. 7, No. DEC.
@article{7dbb95367057415e897130659cc1cbf3,
title = "Dynamic changes in DNA methylation occur during the first Year of life in preterm infants",
abstract = "Preterm birth associates with a substantially increased risk of later cardiovascular disease and neurodevelopmental disorders. Understanding underlying mechanisms will facilitate the development of screening and intervention strategies to reduce disease risk. Changes in DNA methylation have been proposed as one mechanism linking the early environment with later disease risk. We tested the hypothesis that preterm birth associates with altered DNA methylation in genes encoding insulin-like growth factor 2 (IGF2) and FK506-binding protein 5 (FKBP5), which appear particularly vulnerable to early life adversity. Methods: Fifty preterm infants were seen and assessed at birth, term equivalent age, 3 months and 1-year corrected ages; 40 term infants were seen at birth, 3 months and 1 year. Saliva was collected for DNA extraction at birth, term, and 1 year. Pyrosequencing of bisulfite-converted DNA was performed to measure DNA methylation at specific CpG sites within the IGF2 and FKBP5 loci. Results: Weight and head circumference was reduced in preterm infants at all time points. Preterm infants had a higher percentage body fat at term-corrected age, but this difference was not persistent. DNA methylation at the differentially methylated region (DMR) of IGF2 (IGF2DMR2) and FKBP5 was lower in preterm infants at birth- and term-corrected age compared to term infants at birth. IGF2DMR2 and FKBP5 methylation was related to birthweight SD score in preterm infants. Among preterm infants, social deprivation was an independent contributor toward reducing DNA methylation at IGFlDMR2 at birth- and term-corrected age and maternal smoking was associated with reduced DNA methylation at FKBP5 at birth. There were no persistent differences in DNA methylation at 1 year of age. Conclusion: Changes in DNA methylation were identified at key regions of IGF2/H19 and FKBP5 in preterm infants in early life. Potential contributing factors include maternal smoking and social deprivation. However, these changes did not persist at 1 year of age and further longitudinal studies are required to determine any associations between altered DNA methylation in the perinatal period of individuals born preterm and their long-term health.",
keywords = "DNA methylation, FKBP5, Glucocorticoids, IGF2, Prematurity",
author = "Chinthika Piyasena and Jessy Cartier and Nadine Proven{\cc}a and Tobias Wiechmann and Khulan Batbayar and Raju Sunderasan and Gopi Menon and Seckl, {Jonathan R.} and Reynolds, {Rebecca M.} and Binder, {Elisabeth B.} and Drake, {Amanda J.}",
year = "2016",
month = "1",
day = "1",
doi = "10.3389/fendo.2016.00158",
language = "English (US)",
volume = "7",
journal = "Frontiers in Endocrinology",
issn = "1664-2392",
publisher = "Frontiers Media S. A.",
number = "DEC",

}

TY - JOUR

T1 - Dynamic changes in DNA methylation occur during the first Year of life in preterm infants

AU - Piyasena, Chinthika

AU - Cartier, Jessy

AU - Provença, Nadine

AU - Wiechmann, Tobias

AU - Batbayar, Khulan

AU - Sunderasan, Raju

AU - Menon, Gopi

AU - Seckl, Jonathan R.

AU - Reynolds, Rebecca M.

AU - Binder, Elisabeth B.

AU - Drake, Amanda J.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Preterm birth associates with a substantially increased risk of later cardiovascular disease and neurodevelopmental disorders. Understanding underlying mechanisms will facilitate the development of screening and intervention strategies to reduce disease risk. Changes in DNA methylation have been proposed as one mechanism linking the early environment with later disease risk. We tested the hypothesis that preterm birth associates with altered DNA methylation in genes encoding insulin-like growth factor 2 (IGF2) and FK506-binding protein 5 (FKBP5), which appear particularly vulnerable to early life adversity. Methods: Fifty preterm infants were seen and assessed at birth, term equivalent age, 3 months and 1-year corrected ages; 40 term infants were seen at birth, 3 months and 1 year. Saliva was collected for DNA extraction at birth, term, and 1 year. Pyrosequencing of bisulfite-converted DNA was performed to measure DNA methylation at specific CpG sites within the IGF2 and FKBP5 loci. Results: Weight and head circumference was reduced in preterm infants at all time points. Preterm infants had a higher percentage body fat at term-corrected age, but this difference was not persistent. DNA methylation at the differentially methylated region (DMR) of IGF2 (IGF2DMR2) and FKBP5 was lower in preterm infants at birth- and term-corrected age compared to term infants at birth. IGF2DMR2 and FKBP5 methylation was related to birthweight SD score in preterm infants. Among preterm infants, social deprivation was an independent contributor toward reducing DNA methylation at IGFlDMR2 at birth- and term-corrected age and maternal smoking was associated with reduced DNA methylation at FKBP5 at birth. There were no persistent differences in DNA methylation at 1 year of age. Conclusion: Changes in DNA methylation were identified at key regions of IGF2/H19 and FKBP5 in preterm infants in early life. Potential contributing factors include maternal smoking and social deprivation. However, these changes did not persist at 1 year of age and further longitudinal studies are required to determine any associations between altered DNA methylation in the perinatal period of individuals born preterm and their long-term health.

AB - Preterm birth associates with a substantially increased risk of later cardiovascular disease and neurodevelopmental disorders. Understanding underlying mechanisms will facilitate the development of screening and intervention strategies to reduce disease risk. Changes in DNA methylation have been proposed as one mechanism linking the early environment with later disease risk. We tested the hypothesis that preterm birth associates with altered DNA methylation in genes encoding insulin-like growth factor 2 (IGF2) and FK506-binding protein 5 (FKBP5), which appear particularly vulnerable to early life adversity. Methods: Fifty preterm infants were seen and assessed at birth, term equivalent age, 3 months and 1-year corrected ages; 40 term infants were seen at birth, 3 months and 1 year. Saliva was collected for DNA extraction at birth, term, and 1 year. Pyrosequencing of bisulfite-converted DNA was performed to measure DNA methylation at specific CpG sites within the IGF2 and FKBP5 loci. Results: Weight and head circumference was reduced in preterm infants at all time points. Preterm infants had a higher percentage body fat at term-corrected age, but this difference was not persistent. DNA methylation at the differentially methylated region (DMR) of IGF2 (IGF2DMR2) and FKBP5 was lower in preterm infants at birth- and term-corrected age compared to term infants at birth. IGF2DMR2 and FKBP5 methylation was related to birthweight SD score in preterm infants. Among preterm infants, social deprivation was an independent contributor toward reducing DNA methylation at IGFlDMR2 at birth- and term-corrected age and maternal smoking was associated with reduced DNA methylation at FKBP5 at birth. There were no persistent differences in DNA methylation at 1 year of age. Conclusion: Changes in DNA methylation were identified at key regions of IGF2/H19 and FKBP5 in preterm infants in early life. Potential contributing factors include maternal smoking and social deprivation. However, these changes did not persist at 1 year of age and further longitudinal studies are required to determine any associations between altered DNA methylation in the perinatal period of individuals born preterm and their long-term health.

KW - DNA methylation

KW - FKBP5

KW - Glucocorticoids

KW - IGF2

KW - Prematurity

UR - http://www.scopus.com/inward/record.url?scp=85008157711&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85008157711&partnerID=8YFLogxK

U2 - 10.3389/fendo.2016.00158

DO - 10.3389/fendo.2016.00158

M3 - Article

VL - 7

JO - Frontiers in Endocrinology

JF - Frontiers in Endocrinology

SN - 1664-2392

IS - DEC

M1 - 158

ER -