Abstract
Background
Occupational and environmental exposure to lead (Pb) is a persistent health problem majorly in developing countries and has been implied to cause epigenetic alterations. Its effect on histone post-translational modifications is not explored in human population. MicroRNAs are epigenetic modulators reported to be differentially expressed under Pb exposure. The present study was targeted to find plausible association between the role of hsa-miR-146a and global histone (H3) acetylation in Pb-induced inflammation in occupationally exposed workers.
Materials and methods
A total of 100 occupationally exposed individuals working in different industries were recruited for the study and divided into 2 groups based on the median Pb levels [low Pb group (Pb < 5 μg/dL) and High Pb group (Pb > 5 μg/dL)]. The Pb levels were measured in whole blood using atomic absorption spectrometry to confirm Pb exposure. Histone H3 acetylation and serum interleukin-6 (IL-6) levels were measured using colorimetric methods and enzyme-linked immunosorbent assay (ELISA), respectively. MicroRNA-146a expression was quantified using TaqMan assay.
Results
The median BLL of the study population was 5 μg/dL. BLL, IL-6, and Histone (H3) acetylation increased significantly with the duration of exposure. BLL level showed a significant positive correlation with IL-6 and histone H3 acetylation level. We also found that hsa-miR-146a exhibited significantly increased expression in the high Pb group compared to the low Pb group (Fold change: 2.56; P = 0.014). The linear regression model suggested that BLL has significantly predicted histone H3 acetylation, hsa-miR-146a, and IL-6 in the study subjects.
Conclusion
The finding that hsa-miR146a was significantly upregulated in individuals with high BLL and had a significant negative correlation with serum IL-6 suggests that Pb-induced oxidative stress likely activates H3 acetylation, which then releases inflammatory cytokines like IL-6.
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Data availability
The datasets generated during and/or analysed during the current study are not publicly available because of the ongoing project. But the data are available from the corresponding author on reasonable request.
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All authors contributed to the study conception and design. Conceptualisation: SKG, SS; material preparation, data collection and analysis: PVSNKK, SS, SKG, TG, PM; manuscript first draft preparation: PVSNKK, KK,: SKG, SR; writing, review and editing: PVSNKK, SS, KK, SR, PS; sample testing:: SKG, SS; Patient recruiting: SS,: SKG; supervision: SS and PS.
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This study was performed in line with the principles of the Declaration of Helsinki. The present study was approved by the All-India Institute of Medical Sciences, Jodhpur Institutional Ethics Committee. Ethics approval certificate number: AIIMS/IEC/2018/411.
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Kiran, G.S., Kumar, P.K., Mitra, P. et al. Unravelling blood-based epigenetic mechanisms: the impact of hsa-miR-146a and histone H3 acetylation in lead-induced inflammation among occupational workers. Int Arch Occup Environ Health 96, 1257–1266 (2023). https://doi.org/10.1007/s00420-023-02004-4
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DOI: https://doi.org/10.1007/s00420-023-02004-4