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Glutathione S-transferase gene polymorphisms in association with susceptibility to lead toxicity in lead- and cadmium-exposed children near an abandoned lead-zinc mining area in Kabwe, Zambia

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Title: Glutathione S-transferase gene polymorphisms in association with susceptibility to lead toxicity in lead- and cadmium-exposed children near an abandoned lead-zinc mining area in Kabwe, Zambia
Authors: Yohannes, Yared Beyene Browse this author
Nakayama, Shouta M. M. Browse this author →KAKEN DB
Yabe, John Browse this author
Toyomaki, Haruya Browse this author
Kataba, Andrew Browse this author
Nakata, Hokuto Browse this author →KAKEN DB
Muzandu, Kaampwe Browse this author
Ikenaka, Yoshinori Browse this author →KAKEN DB
Choongo, Kennedy Browse this author
Ishizuka, Mayumi Browse this author →KAKEN DB
Keywords: Blood
Children
Lead
Cadmium
GST
Polymorphism
Kabwe
Issue Date: 28-Aug-2021
Publisher: Springer
Journal Title: Environmental science and pollution research
Volume: 29
Issue: 5
Publisher DOI: 10.1007/s11356-021-16098-1
Abstract: Interindividual genetic variations determine human's susceptibility to heavy metal-induced toxicity. Thus, we analyzed blood concentrations of lead (Pb) and cadmium (Cd) in 140 lead-exposed children. Genotyping of the glutathione S-transferase (GST) genes, GSTM1, GSTT1, and GSTP1 genes, was carried out to investigate their possible association with heavy metal concentrations and the risk of susceptibility to Pb toxicity. Exposure to both heavy metals was prevalent among the children. The blood Pb level ranged from 3.30 to 74.0 mu g dL(-1) with an average value of 26.8 mu g dL(-1) that is five times above its reference level. The average Cd level (0.22 mu g L-1) was below its reference level. The metal-gene interaction showed positive correlation between GSTT1 null genotype and Pb and Cd levels (beta = 0.11; p = 0.02 and beta = 0.10; p = 0.01, respectively). More pronounced effects (beta = 0.19; p < 0.01 and beta = 0.25; p = 0.04) were found for the mixture of the three putative genes with blood Pb concentration. The susceptibility analysis using 10 mu g dL(-1) as blood Pb cutoff level showed a high risk of Pb toxicity (OR = 2.54; 95% CI: 1.02-6.32, p = 0.04) for children carrying the GSTP1 Ile/Val genotype. Further, the combined effect of GSTP1 Ile/Val with GSTT1 null genotype was more pronounced and showed an increased risk of susceptibility to Pb toxicity (OR = 11.7; 95% CI: 1.36-102.1, p = 0.02). In summary, this study suggests that GSTT1 null and GSTP1 Ile/Val genotypes are the main genetic factors, and individual and specific combinations of GSTP1 Ile/Val with GSTM1 and GSTT1 GST polymorphisms are associated with susceptibility to Pb toxicity.
Rights: This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: http://dx.doi.org/10.1007/s11356-021-16098-1
Type: article (author version)
URI: http://hdl.handle.net/2115/86627
Appears in Collections:獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 石塚 真由美

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