Human exposure to trichloroethylene is associated with increased variability of blood DNA methylation that is enriched in genes and pathways related to autoimmune disease and cancer.

Abstract

Human exposure to trichloroethylene (TCE) is linked to kidney cancer, autoimmune diseases, and probably non-Hodgkin lymphoma. Additionally, TCE exposed mice and cell cultures show altered DNA methylation. To evaluate associations between TCE exposure and DNA methylation in humans, we conducted an epigenome-wide association study (EWAS) in TCE exposed workers using the HumanMethylation450 BeadChip. Across individual CpG probes, genomic regions, and globally (i.e., the 450K methylome), we investigated differences in mean DNA methylation and differences in variability of DNA methylation between 73 control (< 0.005 ppm TCE), 30 lower exposed (< 10 ppm TCE), and 37 higher exposed ( ≥ 10 ppm TCE) subjects' white blood cells. We found that TCE exposure increased methylation variation globally (Kruskal-Wallis p-value = 3.75e-3) and in 25 CpG sites at a genome-wide significance level (Bonferroni p-value < 0.05). We identified a 609 basepair region in the TRIM68 gene promoter that exhibited hypomethylation with increased exposure to TCE (FWER = 1.20e-2). Also, genes that matched to differentially variable CpGs were enriched in the 'focal adhesion' biological pathway (p-value = 2.80e-2). All in all, human exposure to TCE was associated with epigenetic alterations in genes involved in cell-matrix adhesions and interferon subtype expression, which are important in the development of autoimmune diseases; and in genes related to cancer development. These results suggest that DNA methylation may play a role in the pathogenesis of TCE exposure-related diseases and that TCE exposure may contribute to epigenetic drift.

• Authors: Rachael V Phillips, Linda Rieswijk, Alan E Hubbard, Roel Vermeulen, Jinming Zhang, Wei Hu, Laiyu Li, Bryan A Bassig, Jason Y Y Wong, Boris Reiss, Yongshun Huang, Cuiju Wen, Mark Purdue, Xiaojiang Tang, Luoping Zhang, Martyn T Smith, Nathaniel Rothman, Qing Lan
• Journal: Epigenetics (Epigenetics) Vol. 14 Issue 11 Pg. 1112-1124 (11 2019) ISSN: 1559-2308 [Electronic] United States
• PMID: 31241004 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantigens
• Tripartite Motif Proteins
• Trichloroethylene
• TRIM68 protein, human
• Ubiquitin-Protein Ligases

Topics

• Adult
• Autoantigens (genetics)
• Autoimmune Diseases (genetics)
• CpG Islands
• DNA Methylation
• Female
• Genetic Loci
• Genetic Predisposition to Disease
• Genetic Variation
• Humans
• Male
• Neoplasms (genetics)
• Trichloroethylene (pharmacology)
• Tripartite Motif Proteins (genetics)
• Ubiquitin-Protein Ligases (genetics)