Methylation profiles of global LINE-1 DNA and the GSTP1 promoter region in children exposed to lead (Pb)

Epigenetics. 2022 Dec;17(13):2377-2388. doi: 10.1080/15592294.2022.2123924. Epub 2022 Sep 21.

Abstract

Lead (Pb) exposure has adverse health effects and altered DNA methylation may contribute to Pb toxicity. LINE-1 is an interspersed repeated DNA that is used as a surrogate marker for estimating genomic DNA methylation levels, and GSTP1 is an isozyme that detoxifies xenobiotics like Pb, and its expression is inhibited by methylation. Thus, to assess the effects of Pb exposure on global hypomethylation and gene-specific promoter hypermethylation, we examined DNA methylation at LINE-1 repetitive elements and the GSTP1 promoter region. Blood samples were obtained from children (N = 123) living in Pb-polluted areas (as exposed children) and children (N = 63) living in Pb-unpolluted areas (as control children) in Kabwe, Zambia. ICP-MS was used to determine blood lead levels (BLLs), and pyrosequencing and a fluorescence-based polymerase chain reaction assay were used to determine levels of LINE-1 methylation and GSTP1 promoter methylation, respectively. Inverse association was found between BLLs and LINE-1 methylation (β = - 0.046, p = 0.006). The highest quartile of BLL had significant hypomethylation of LINE-1 (p for trend = 0.03), suggesting the higher the BLL, the lower LINE-1 methylation. GSTP1 methylation levels did not differ significantly between the two areas (p = 0.504), nor was it associated with Pb poisoning risk (OR = 1.03, p = 0.476), indicating GSTP1 methylation may not be a reliable biomarker of Pb exposure in healthy people. Therefore, Pb-related health problems could result from global DNA methylation changes due to high BLLs.

Keywords: Blood lead; DNA methylation; GSTP1; LINE-1; children.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Child
  • DNA
  • DNA Methylation
  • Glutathione S-Transferase pi / genetics
  • Humans
  • Lead Poisoning* / genetics
  • Lead* / toxicity
  • Promoter Regions, Genetic

Substances

  • Lead
  • Glutathione S-Transferase pi
  • DNA
  • Biomarkers
  • GSTP1 protein, human

Grants and funding

This study was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan awarded to M. Ishizuka (Nos. 16H01779, 18K19847, 18KK0287, 21H04919), Y. Ikenaka (18H04132), and S.M.M. Nakayama (Nos. 17KK0009 and 20K20633). This work was also supported by the foundation of Bilateral Open Partnership Joint Research Projects (JPJSBP120209902; SMMN). This work was also supported by JSPS CORE to CORE program (MI), The Japan Prize Foundation.; Hokkaido University’s SOUSEI Support Program for Young Researchers in FY2020 (SMMN); and Hokkaido University SOUSEI TOKUTEI Specific Research Projects (MI). This research was also supported by JST/JICA, SATREPS (Science and Technology Research Partnership for Sustainable Development; No. JPMJSA1501), aXis (Accelerating Social Implementation for SDGs Achievement; No. JPMJAS2001) and Japan Science and Technology Agency AJ-CORE Project (MI) funded by JST as well as Program for supporting introduction of the new sharing system (JPMXS0420100619; JSPS; Japanese Ministry of Education Culture, Sports, Science and Technology 17KK0009, 20K20633.