Arsenic exposure and human blood DNA methylation and hydroxymethylation profiles in two diverse populations from Bangladesh and Spain

• Published in: Environmental research Vol. 204; no. Pt B; p. 112021
• Main Authors: Domingo-Relloso, Arce, Bozack, Anne, Kiihl, Samara, Rodriguez-Hernandez, Zulema, Rentero-Garrido, Pilar, Casasnovas, J. Antonio, Leon-Latre, Montserrat, Garcia-Barrera, Tamara, Gomez-Ariza, J. Luis, Moreno, Belen, Cenarro, Ana, de Marco, Griselda, Parvez, Faruque, Siddique, Abu B., Shahriar, Hasan, Uddin, Mohammad N., Islam, Tariqul, Navas-Acien, Ana, Gamble, Mary, Tellez-Plaza, Maria
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.03.2022
• Subjects: Arsenic; Arsenic - toxicity; Bangladesh; DNA hydroxymethylation; DNA Methylation; Epigenesis, Genetic; Epigenetics; Humans; Lectins, C-Type; Male; Nuclear Proteins; Receptors, Mitogen; Spain; Bangladesh; Spain; DNA methylation; Epigenetics; DNA hydroxymethylation; Arsenic
• ISSN: 0013-9351; 1096-0953
• DOI: 10.1016/j.envres.2021.112021

Associations of arsenic (As) with the sum of 5-mC and 5-hmC levels have been reported; however, As exposure-related differences of the separated 5-mC and 5-hmC markers have rarely been studied. In this study, we evaluated the association of arsenic exposure biomarkers and 5-mC and 5-hmC in 30 healthy men (43–55 years) from the Aragon Workers Health Study (AWHS) (Spain) and 31 healthy men (31–50 years) from the Folic Acid and Creatinine Trial (FACT) (Bangladesh). We conducted 5-mC and 5-hmC profiling using Infinium MethylationEPIC arrays, on paired standard and modified (ox-BS in AWHS and TAB in FACT) bisulfite converted blood DNA samples. The median for the sum of urine inorganic and methylated As species (ΣAs) (μg/L) was 12.5 for AWHS and 89.6 for FACT. The median of blood As (μg/L) was 8.8 for AWHS and 10.2 for FACT. At a statistical significance p-value cut-off of 0.01, the differentially methylated (DMP) and hydroxymethylated (DHP) positions were mostly located in different genomic sites. Several DMPs and DHPs were consistently found in AWHS and FACT both for urine ΣAs and blood models, being of special interest those attributed to the DIP2C gene. Three DMPs (annotated to CLEC12A) for AWHS and one DHP (annotated to NPLOC4) for FACT remained statistically significant after false discovery rate (FDR) correction. Pathways related to chronic diseases including cardiovascular, cancer and neurological were enriched. While we identified common 5-hmC and 5-mC signatures in two populations exposed to varying levels of inorganic As, differences in As-related epigenetic sites across the study populations may additionally reflect low and high As-specific associations. This work contributes a deeper understanding of potential epigenetic dysregulations of As. However, further research is needed to confirm biological consequences associated with DIP2C epigenetic regulation and to investigate the role of 5-hmC and 5-mC separately in As-induced health disorders at different exposure levels. •We evaluated the association between arsenic (As) biomarkers with CpG-specific blood DNA methylation and hydroxymethylation in two study populations with high and low As exposure.•As-related differentially methylated and hydroxymethylated positions were mostly located in different genomic positions.•We observed strongly suggestive As-related epigenetic signatures in common in the two populations, of special interest CpGs annotated to the DIP2C gene .•Other epigenetic marks were associated with As in only one of the study populations, suggesting a potential dependency upon As exposure dose in specific genomic sites.