Lead Exposure during Early Human Development and DNA Methylation of Imprinted Gene Regulatory Elements in Adulthood [electronic resource]

 0 Người đánh giá. Xếp hạng trung bình 0

Tác giả:

Ngôn ngữ: eng

Ký hiệu phân loại: 574. [Unassigned]

Thông tin xuất bản: Oak Ridge, Tenn. : Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2015

Mô tả vật lý: Size: p. 666-673 : , digital, PDF file.

Bộ sưu tập: Metadata

ID: 261119

 Here, 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. 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. 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. Mean blood lead concentration from birth to 78 months was associated with a significant decrease in PEG3 DMR methylation (? = ?0.0014
  95% CI: ?0.0023, ?0.0005, p = 0.002), stronger in males (? = ?0.0024
  95% CI: ?0.0038, ?0.0009, p = 0.003) than in females (? = ?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 (? = ?0.0013
  95% CI: ?0.0023, ?0.0003, p = 0.01) DMR methylation, but primarily in females, (? = ?0.0017
  95% CI: ?0.0029, ?0.0006, p = 0.005) rather than in males, (? = ?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 (? = 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. Our findings provide evidence that early childhood lead exposure results in sexdependent and gene-specific DNA methylation differences in the DMRs of PEG3, IGF2/H19, and PLAGL1/HYMAI in adulthood.
Tạo bộ sưu tập với mã QR

THƯ VIỆN - TRƯỜNG ĐẠI HỌC CÔNG NGHỆ TP.HCM

ĐT: (028) 71010608 | Email: tt.thuvien@hutech.edu.vn

Copyright @2024 THƯ VIỆN HUTECH