Prenatal lead exposure is associated with decreased cord blood DNA methylation of the glycoprotein VI gene involved in platelet activation and thrombus formation

Environmental Epigenetics
K EngströmKarin Broberg

Abstract

Early-life lead exposure impairs neurodevelopment and later exposure affects the cardiovascular system. Lead has been associated with reduced global 5-methylcytosine DNA methylation, suggesting that lead toxicity acts through epigenetic mechanisms. The objective of this study is to clarify how early-life lead exposure alters DNA methylation of specific genes, using an epigenomic approach. We measured lead concentrations in urine [gestational week (GW), 8] and erythrocytes (GW 14), using inductively coupled plasma mass spectrometry, for 127 pregnant mothers recruited in the MINIMat food and supplementation cohort in rural Bangladesh. Cord blood DNA methylation was analyzed with the Infinium HumanMethylation450K BeadChip, and top sites were validated by methylation-sensitive high-resolution melt curve analysis. Maternal urinary lead concentrations (divided into quartiles) showed significant (after adjustment for false discovery rate) inverse associations with methylation at nine CpGs. Three of these sites were in the 5'-end, including the promoter, of glycoprotein IV (GP6); cg18355337 (q = 0.029,β = -0.30), cg25818583 (q = 0.041,β = -0.18), and cg23796967 (q = 0.047,β = -0.17). The methylation in another CpG site inGP6was close t...Continue Reading

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Citations

Jul 5, 2019·Reviews on Environmental Health·Chinonye Doris OnuzuluSolomon Oladapo Rotimi
May 24, 2019·Human & Experimental Toxicology·M S ManiH S Dsouza
Oct 20, 2018·International Journal of Environmental Research and Public Health·Kinga PolanskaGemma Calamandrei
Dec 17, 2020·Environmental Epigenetics·Jonathan A HeissAllan C Just
Mar 4, 2021·Environmental Science and Pollution Research International·Rui YanAndy T Y Lau
Jan 4, 2021·Endocrine Reviews·Vasantha PadmanabhanMuraly Puttabyatappa
Apr 3, 2021·Epigenetics : Official Journal of the DNA Methylation Society·Max T AungM Daniele Fallin

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Methods Mentioned

BETA
density gradient centrifugation
PCA

Software Mentioned

UCSC genome browser
R package limma
bumphunter
MINIMat
ComBat
R package minfi
sva

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