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Dynamic Changes in DNA Methylation Occur during the First Year of Life in Preterm Infants
Chinthika Piyasena1, Jessy Cartier2, Nadine Provençal3
1British Heart Foundation Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK; Neonatal Unit, Simpson Centre for Reproductive Health, Royal Infirmary of Edinburgh, Edinburgh, UK.
Insights
Preterm birth is linked to altered DNA methylation in IGF2 and FKBP5 genes in early life, potentially influenced by social deprivation and maternal smoking. These epigenetic changes were not persistent at one year.
Area of Science:
- Epigenetics
- Developmental Biology
- Perinatal Medicine
Background:
- Preterm birth increases risks for cardiovascular disease and neurodevelopmental disorders.
- DNA methylation changes are a proposed mechanism linking early environment to later disease.
- Insulin-like growth factor 2 (IGF2) and FK506-binding protein 5 (FKBP5) genes are vulnerable to early life adversity.
Purpose of the Study:
- To investigate if preterm birth is associated with altered DNA methylation in IGF2 and FKBP5 genes.
- To explore potential early life factors influencing these epigenetic changes.
Main Methods:
- Compared DNA methylation in 50 preterm and 40 term infants at birth, term-corrected age, and 1-year corrected age.
- Collected saliva for DNA extraction and used pyrosequencing to measure methylation at specific CpG sites in IGF2 and FKBP5 loci.
- Assessed associations with birthweight, social deprivation, and maternal smoking.
Main Results:
- Preterm infants showed lower DNA methylation at IGF2DMR2 and FKBP5 at birth and term-corrected age compared to term infants.
- Methylation levels correlated with birthweight SD score in preterm infants.
- Social deprivation and maternal smoking were associated with reduced DNA methylation in early life, but differences were not present at 1 year.
Conclusions:
- Early life DNA methylation changes in IGF2/H19 and FKBP5 were observed in preterm infants.
- Maternal smoking and social deprivation may contribute to these epigenetic alterations.
- Longitudinal studies are needed to confirm associations with long-term health outcomes.
Background:
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 IGF2DMR2 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.
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