Background: Lead exposure during early development causes neurodevelopmental disorders by unknown mechanisms. Epidemiologic studies have focused recently on determining associations between lead exposure and global DNA methylation; however, such approaches preclude the identification of loci that may alter human disease risk.
Objectives: The objective of this study was to determine whether maternal, postnatal, and early childhood lead exposure can alter the differentially methylated regions (DMRs) that control the monoallelic expression of imprinted genes involved in metabolism, growth, and development.
Methods: Questionnaire data and serial blood lead levels were obtained from 105 participants (64 females, 41 males) of the Cincinnati Lead Study from birth to 78 months. When participants were adults, we used Sequenom EpiTYPER assays to test peripheral blood DNA to quantify CpG methylation in peripheral blood leukocytes at DMRs of 22 human imprinted genes. Statistical analyses were conducted using linear regression.
Results: Mean blood lead concentration from birth to 78 months was associated with a significant decrease in PEG3 DMR methylation (β = −0.0014; 95% CI: −0.0023, −0.0005, p = 0.002), stronger in males (β = −0.0024; 95% CI: −0.0038, −0.0009, p = 0.003) than in females (β = −0.0009; 95% CI: −0.0020, 0.0003, p = 0.1). Elevated mean childhood blood lead concentration was also associated with a significant decrease in IGF2/H19 (β = −0.0013; 95% CI: −0.0023, −0.0003, p = 0.01) DMR methylation, but primarily in females, (β = −0.0017; 95% CI: −0.0029, −0.0006, p = 0.005) rather than in males, (β = −0.0004; 95% CI: −0.0023, 0.0015, p = 0.7). Elevated blood lead concentration during the neonatal period was associated with higher PLAGL1/HYMAI DMR methylation regardless of sex (β = 0.0075; 95% CI: 0.0018, 0.0132, p = 0.01). The magnitude of associations between cumulative lead exposure and CpG methylation remained unaltered from 30 to 78 months.
Conclusions: Our findings provide evidence that early childhood lead exposure results in sex-dependent and gene-specific DNA methylation differences in the DMRs of PEG3, IGF2/H19, and PLAGL1/HYMAI in adulthood.
1Department of Community and Family Medicine, and 2Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina, USA; 3Division of Epidemiology and Biostatistics, Department of Environmental Health, Center for Clinical and Translational Science and Training, University of Cincinnati (UC), Cincinnati, Ohio, USA; 4Department of Biological Sciences, Center for Human Health and the Environment, North Carolina State University (NCSU), Raleigh, North Carolina, USA; 5Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA; 6Cincinnati Children’s Environmental Health Center, Cincinnati Children’s Hospital Medical Center, UC College of Medicine, Cincinnati, Ohio, USA; 7Department of Radiology, 8Department of Pediatrics, 9Department of Environmental Health, 10Center for Environmental Genetics, and 11Division of Epidemiology and Biostatistics, UC College of Medicine, Cincinnati, Ohio, USA; 12Department of Oncology, McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, Wisconsin, USA; 13Department of Sport and Exercise Sciences, Institute of Sport and Physical Activity Research, University of Bedfordshire, Bedford, Bedfordshire, United Kingdom
Recommended Citation:
Yue Li,1,2* Changchun Xie,et al. Lead Exposure during Early Human Development and DNA Methylation of Imprinted Gene Regulatory Elements in Adulthood[J]. Environmental Health Perspectives,2016-01-01,Volume 124(Issue 5):666