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. 2023 Jan 4:13:1043486.
doi: 10.3389/fgene.2022.1043486. eCollection 2022.

Association of environmental exposure to chromium with differential DNA methylation: An epigenome-wide study

Meiduo Zhao  1   2 , Jingtao Wu  1   2 , Jing Xu  1   2 , Ang Li  1   2 , Yayuan Mei  1   2 , Xiaoyu Ge  1   2 , Guohuan Yin  1   2 , Xiaolin Liu  3 , Lanping Wei  4 , Qun Xu  1   2
Affiliations

Association of environmental exposure to chromium with differential DNA methylation: An epigenome-wide study

Meiduo Zhao et al. Front Genet. .

Abstract

Introduction: Previous studies have reported that chromium (Cr)-induced epigenetic alterations and DNA methylation play a vital role in the pathogenesis of diseases induced by chromium exposure. Epigenomic analyses have been limited and mainly focused on occupational chromium exposure; their findings are not generalizable to populations with environmental Cr exposure. Methods: We identified the differential methylation of genes and regions to elucidate the mechanisms of toxicity related to environmental chromium exposure. DNA methylation was measured in blood samples collected from individuals in Cr-contaminated (n = 10) and unexposed areas (n = 10) by using the Illumina Infinium HumanMethylation850K array. To evaluate the relationship between chromium levels in urine and CpG methylation at 850 thousand sites, we investigated differentially methylated positions (DMPs) and differentially methylated regions (DMRs) by using linear models and DMRcate method, respectively. The model was adjusted for biologically relevant variables and estimated cell-type compositions. Results: At the epigenome-wide level, we identified five CpGs [cg20690919 (p FDR =0.006), cg00704664 (p FDR =0.024), cg10809143 (p FDR =0.043), cg27057652 (p FDR =0.047), cg05390480 (p FDR =0.024)] and one DMR (chr17: 19,648,718-19,648,972), annotated to ALDH3A1 genes (p < 0.05) as being significantly associated with log2 transformed urinary chromium levels. Discussion: Environmental chromium exposure is associated with DNA methylation, and the significant DMPs and DMR being annotated to cause DNA damage and genomic instability were found in this work. Research involving larger samples is required to further explore the epigenetic effect of environmental chromium exposure on health outcomes through DNA methylation.

Keywords: DNA methylation; Illumina 850K; chromate; epigenetics; epigenome-wide association study.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Manhattan plot for epigenome-wide association of log2 transformed urinary Cr concentration and DNA methylation levels. Full models were adjusted for sex, smoking status, BMI, urine creatinine level, age at enrollment, and estimated cell-type proportions. The solid red line represents the Bonferroni cutoff, and the dashed line represents the FDR cutoff.
FIGURE 2
FIGURE 2
Volcano plot for the epigenome-wide association of log2 transformed urinary Cr concentration and DNA methylation levels. Full models were adjusted for sex, smoking status, BMI, urine creatinine level, age at enrollment, and estimated cell-type proportions. The solid red line represents the Bonferroni cutoff, and the dashed line represents the FDR cutoff.
FIGURE 3
FIGURE 3
DMR associated with Cr located within chr17: 19,648,718–19,648,972. Percentage difference in methylation estimated from limma models of beta values adjusted for sex, smoking status, BMI, urine creatinine level, age at enrollment, and estimated cell-type proportions.
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