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Published on: July 12, 2012
Examination of DNA Methylation Patterns in Children Born Premature with Prenatal Tobacco Smoke Exposure
Olivia E Gittens1, Alonzo T Folger2, Xue Zhang3
1Medical Scientist Training Program, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
Insights
Prenatal tobacco smoke exposure (TSE) alters DNA methylation (DNAm) in preterm children. This pilot study used RRBS to identify specific gene methylation changes linked to neurodevelopment.
Area of Science:
- Epigenetics and Developmental Biology
- Environmental Health
- Genomics
Background:
- Prenatal tobacco smoke exposure (TSE) is linked to epigenetic alterations, specifically DNA methylation (DNAm).
- These DNAm changes may have functional consequences for child development.
- Understanding these epigenetic impacts is crucial for early intervention and prevention strategies.
Purpose of the Study:
- To investigate differential DNA methylation patterns in preterm children with and without prenatal TSE.
- To utilize reduced representation bisulfite sequencing (RRBS) for a comprehensive analysis of DNAm sites.
- To identify specific genes and genomic regions affected by prenatal TSE.
Main Methods:
- Collected buccal swabs from 16 two-year-old children (7 with TSE, 9 without).
- Quantified DNAm at over 1.3 million CpG sites using RRBS.
- Employed Bayesian beta-binomial hierarchical regression models and False Discovery Rate correction for differential methylation analysis.
Main Results:
- Identified significant differential methylation at CpG sites within intronic regions of CALN1 and LINGO1 genes.
- Detected differential methylation in the distal intergenic region of the TBL1XR1 gene.
- These findings suggest prenatal TSE influences epigenetic regulation in neurodevelopment-related genes.
Conclusions:
- Prenatal TSE may lead to specific DNA methylation changes in genes associated with neurodevelopment.
- RRBS is a valuable tool for discovering novel DNAm changes related to environmental exposures.
- Larger studies are needed to validate and expand upon these preliminary findings.
Abstract:
Prenatal tobacco smoke exposure (TSE) has been associated with significant alterations in DNA methylation (DNAm), an epigenetic mechanism with potential functional consequences to child development. This pilot study aimed to investigate differential DNAm patterns in preterm children with and without prenatal TSE using reduced representation bisulfite sequencing (RRBS) to interrogate a wider array of sites than in more common approaches, namely microarrays. Buccal swabs were collected from 16 two-year-old children (7 with TSE, 9 without), and DNAm was quantified at over 1.3 million CpG sites. To identify differential DNAm, univariable analyses were first performed and followed by Bayesian beta-binomial hierarchical regression models for sequence count data including adjustment for potential confounders. False Discovery Rate correction was used to account for multiple comparisons. Significant differential methylation was observed at CpG sites within intronic regions of the CALN1 and LINGO1 genes and the distal intergenic region of the TBL1XR1 gene. These findings suggest that prenatal TSE may influence epigenetic regulation in genes involved in neurodevelopment. This study demonstrates the importance of RRBS in identifying novel DNAm changes associated with prenatal TSE and highlights the need for larger studies to validate and expand upon these preliminary findings.
