Long-term environmental metal exposure is associated with hypomethylation of CpG sites in NFKB1 and other genes related to oncogenesis

Clinical Epigenetics

Research

Anna Petrackova¹  Eva Kriegova¹  Jakub Savara²  Ani Stepanyan³  Siras Hakobyan³  Suren Davitavyan³  Arsen Arakelyan³ 

[1] Department of Immunology, Faculty of Medicine and Dentistry, Palacký University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic;Department of Immunology, Faculty of Medicine and Dentistry, Palacký University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic;Department of Computer Science, Faculty of Electrical Engineering and Computer Science, VSB-Technical University of Ostrava, Ostrava, Czech Republic;Institute of Molecular Biology, National Academy of Sciences, Yerevan, Republic of Armenia;

关键词: Toxic metal;    Environmental exposure;    DNA methylation;    NFKB1;    CDKN2A;    IGF2;    ESR1;    Uranium;   

DOI  :  10.1186/s13148-023-01536-3

 received in 2023-04-19, accepted in 2023-07-20,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundLong-term environmental exposure to metals leads to epigenetic changes and may increase risks to human health. The relationship between the type and level of metal exposure and epigenetic changes in subjects exposed to high concentrations of metals in the environment is not yet clear. The aim of our study is to find the possible association of environmental long-term exposure to metals with DNA methylation changes of genes related to immune response and carcinogenesis. We investigated the association of plasma levels of 21 essential and non-essential metals detected by ICP-MS and the methylation level of 654 CpG sites located on NFKB1, CDKN2A, ESR1, APOA5, IGF2 and H19 genes assessed by targeted bisulfite sequencing in a cohort of 40 subjects living near metal mining area and 40 unexposed subjects. Linear regression was conducted to find differentially methylated positions with adjustment for gender, age, BMI class, smoking and metal concentration.ResultsIn the metal-exposed group, five CpGs in the NFKB1 promoter region were hypomethylated compared to unexposed group. Four differentially methylated positions (DMPs) were associated with multiple metals, two of them are located on NFKB1 gene, and one each on CDKN2A gene and ESR1 gene. Two DMPs located on NFKB1 (chr4:102500951, associated with Be) and IGF2 (chr11:2134198, associated with U) are associated with specific metal levels. The methylation status of the seven CpGs located on NFKB1 (3), ESR1 (2) and CDKN2A (2) positively correlated with plasma levels of seven metals (As, Sb, Zn, Ni, U, I and Mn).ConclusionsOur study revealed methylation changes in NFKB1, CDKN2A, IGF2 and ESR1 genes in individuals with long-term human exposure to metals. Further studies are needed to clarify the effect of environmental metal exposure on epigenetic mechanisms and pathways involved.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023. corrected publication 2023

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