Methylation profiles of global LINE-1 DNA and the GSTP1 promoter region in children exposed to lead (Pb)
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 expre...
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Format: | Article |
Language: | English |
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Taylor & Francis Group
2022-12-01
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Series: | Epigenetics |
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Online Access: | http://dx.doi.org/10.1080/15592294.2022.2123924 |
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author | Yared Beyene Yohannes Shouta M.M. Nakayama John Yabe Haruya Toyomaki Andrew Kataba Hokuto Nakata Kaampwe Muzandu Chihiro Miyashita Yoshinori Ikenaka Kennedy Choongo Mayumi Ishizuka |
author_facet | Yared Beyene Yohannes Shouta M.M. Nakayama John Yabe Haruya Toyomaki Andrew Kataba Hokuto Nakata Kaampwe Muzandu Chihiro Miyashita Yoshinori Ikenaka Kennedy Choongo Mayumi Ishizuka |
author_sort | Yared Beyene Yohannes |
collection | DOAJ |
description | 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. |
first_indexed | 2024-03-11T23:05:15Z |
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id | doaj.art-2ac08ec24c5442c5b75385579f8abd5d |
institution | Directory Open Access Journal |
issn | 1559-2294 1559-2308 |
language | English |
last_indexed | 2024-03-11T23:05:15Z |
publishDate | 2022-12-01 |
publisher | Taylor & Francis Group |
record_format | Article |
series | Epigenetics |
spelling | doaj.art-2ac08ec24c5442c5b75385579f8abd5d2023-09-21T13:23:12ZengTaylor & Francis GroupEpigenetics1559-22941559-23082022-12-0117132377238810.1080/15592294.2022.21239242123924Methylation profiles of global LINE-1 DNA and the GSTP1 promoter region in children exposed to lead (Pb)Yared Beyene Yohannes0Shouta M.M. Nakayama1John Yabe2Haruya Toyomaki3Andrew Kataba4Hokuto Nakata5Kaampwe Muzandu6Chihiro Miyashita7Yoshinori Ikenaka8Kennedy Choongo9Mayumi Ishizuka10Hokkaido UniversityHokkaido UniversityThe University of ZambiaHokkaido UniversityThe University of ZambiaHokkaido UniversityThe University of ZambiaHokkaido UniversityHokkaido UniversityThe University of ZambiaHokkaido UniversityLead (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.http://dx.doi.org/10.1080/15592294.2022.2123924blood leadchildrendna methylationgstp1line-1 |
spellingShingle | Yared Beyene Yohannes Shouta M.M. Nakayama John Yabe Haruya Toyomaki Andrew Kataba Hokuto Nakata Kaampwe Muzandu Chihiro Miyashita Yoshinori Ikenaka Kennedy Choongo Mayumi Ishizuka Methylation profiles of global LINE-1 DNA and the GSTP1 promoter region in children exposed to lead (Pb) Epigenetics blood lead children dna methylation gstp1 line-1 |
title | Methylation profiles of global LINE-1 DNA and the GSTP1 promoter region in children exposed to lead (Pb) |
title_full | Methylation profiles of global LINE-1 DNA and the GSTP1 promoter region in children exposed to lead (Pb) |
title_fullStr | Methylation profiles of global LINE-1 DNA and the GSTP1 promoter region in children exposed to lead (Pb) |
title_full_unstemmed | Methylation profiles of global LINE-1 DNA and the GSTP1 promoter region in children exposed to lead (Pb) |
title_short | Methylation profiles of global LINE-1 DNA and the GSTP1 promoter region in children exposed to lead (Pb) |
title_sort | methylation profiles of global line 1 dna and the gstp1 promoter region in children exposed to lead pb |
topic | blood lead children dna methylation gstp1 line-1 |
url | http://dx.doi.org/10.1080/15592294.2022.2123924 |
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