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 μg dL-1 with an average value of 26.8 μg dL-1 that is five times above its reference level. The average Cd level (0.22 μg L-1) was below its reference level. The metal-gene interaction showed positive correlation between GSTT1 null genotype and Pb and Cd levels (β = 0.11; p = 0.02 and β = 0.10; p = 0.01, respectively). More pronounced effects (β = 0.19; p < 0.01 and β = 0.25; p = 0.04) were found for the mixture of the three putative genes with blood Pb concentration. The susceptibility analysis using 10 μg 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.
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Acknowledgements
We are very grateful to the children that participated in this study and the laboratory technicians and nurses at the five health centers in Kabwe. We are also grateful to the Kabwe District Health Office, Kabwe Municipal Council and the Ministry of Health, Zambia, for facilitating our work. Our appreciation is extended to Takahiro Ichise and Nagisa Hirano for their technical support.
Funding
This work was supported by the Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan awarded to M. Ishizuka (Nos. 16H0177906, 18K1984708, 18KK028708, 21H02351), Ikenaka (18H0413208), and S.M.M. Nakayama (Nos. 17KK0009 and 20K20633). This work was also supported by the foundation of JSPS 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 Specific Research Projects (MI). This research was also supported by JST/JICA, SATREPS (Science and Technology Research Partnership for Sustainable Development; No. JPMJSA1501) and aXis (Accelerating Social Implementation for SDGs Achievement; No. JPMJAS2001) funded by JST as well as Program for supporting introduction of the new sharing system (JPMXS0420100619).
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YBY: Responsible for conceptualization, data analysis, investigation, methodology, and writing both drafting the original paper and reviewing.
SMMN: Responsible for conceptualization, analysis, funding acquisition, investigation, and writing and corresponding author.
JY, HN, HT, AK and KM: Participate in sample collection, material preparation, and reviewing the manuscript.
YK: Funding acquisition and supervision.
KC: Supervision.
MI: Responsible for project administration, funding acquisition, supervision, and reviewing the manuscript and corresponding author.
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Study protocol approval and permission to conduct the research were obtained from the University of Zambia Research Ethics Committee (UNZAREC; REF. No. 012-04-16) and the Ministry of Health Zambia, respectively. Material transfer agreement (MTA, Approval No. E00417) has been issued from the Ministry of Health, Zambia, for transporting frozen samples to Japan.
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Yohannes, Y.B., Nakayama, S.M.M., Yabe, J. et al. 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. Environ Sci Pollut Res 29, 6622–6632 (2022). https://doi.org/10.1007/s11356-021-16098-1
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DOI: https://doi.org/10.1007/s11356-021-16098-1