Novel DNA Methylation Biomarkers for Hexavalent Chromium Exposure: An Epigenome-Wide Analysis

Abstract

Aim: We aimed to identify differential methylation of genes that could illuminate the biological mechanisms of chromium (VI) toxicity in this exposure-control study. Materials & methods: DNA methylation was measured in blood samples collected from electroplating workers and controls using a combination of Infinium Methylation450K Chip and targeted-bisulfite sequencing. QuantiGene assay was used to detect the mRNA expression of differentially methylated genes. Inductively coupled plasma–mass spectrometry was used to quantify metals in blood and urine samples. The cytosine–phosphate–guanine sites methylation and gene expression were confirmed in a human lymphoblastoid cell line. Results & conclusion: A total of 131 differentially methylated cytosine–phosphate–guanine sites were found between exposures and controls. DNA methylation of SEMA4B may serve as a potential biomarker for chromium (VI) exposure.

Graphical abstract

Keywords::

• Cr(VI)-exposed populations
• DNA methylation
• gene expression
• Illumina 450K
• targeted-bisulfite sequencing

Each author’s contribution to this article is as following: L Feng contributed to the study concept and design, acquisition of data, drafting of the manuscript, statistical analysis and revision of the manuscript; X Guo performed the genome-scale methylation data; T Li was responsible for the targeted-bisulfite sequencing data; C Yao and H Xia were responsible for the metal experimental data; Z Jiang and J Jia performed the statistical analysis; Y Fang and L Shi were responsible for the cell culture and treatments; C(A) Lu was responsible for the revision of the manuscript; J Lou performed the study design and supervision, obtained funding, and administrative support.

Financial & competing interests disclosure

This work was supported by the National Natural Science Foundation of China (nos. 81472960, 81001242, 81502794), Zhejiang Provincial Program for the Cultivation of High-level Innovative Health talents (2014) and Zhejiang Medical Health Science and Technology Foundation (2017KY301, 2019PY024). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No funded writing assistance been used in the creation of this manuscript.

Ethical conduct of research

This study was approved by Zhejiang Academy of Medical Sciences Ethical Committee, and informed consent has been obtained from the participants involved.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (nos. 81472960, 81001242, 81502794), Zhejiang Provincial Program for the Cultivation of High-level Innovative Health talents (2014) and Zhejiang Medical Health Science and Technology Foundation (2017KY301, 2019PY024). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No funded writing assistance been used in the creation of this manuscript.