title: Gene-specific differential DNA methylation and chronic arsenic exposure in an epigenome-wide association study of adults in Bangladesh.
abstract: BACKGROUND
  Inorganic arsenic is one of the most common naturally occurring contaminants found in the environment. Arsenic is associated with a number of health outcomes, with epigenetic modification suggested as a potential mechanism of toxicity.
  
  
  OBJECTIVE
  Among a sample of 400 adult participants, we evaluated the association between arsenic exposure, as measured by blood and urinary total arsenic concentrations, and epigenome-wide white blood cell DNA methylation.
  
  
  METHODS
  We used linear regression models to examine the associations between arsenic exposure and methylation at each CpG site, adjusted for sex, age, and batch. Differentially methylated loci were subsequently examined in relation to corresponding gene expression for functional evidence of gene regulation.
  
  
  RESULTS
  In adjusted analyses, we observed four differentially methylated CpG sites with urinary total arsenic concentration and three differentially methylated CpG sites with blood arsenic concentration, based on the Bonferroni-corrected significance threshold of p < 1 × 10(-7). Methylation of PLA2G2C (probe cg04605617) was the most significantly associated locus in relation to both urinary (p = 3.40 × 10(-11)) and blood arsenic concentrations (p = 1.48 × 10(-11)). Three additional novel methylation loci-SQSTM1 (cg01225779), SLC4A4 (cg06121226), and IGH (cg13651690)--were also significantly associated with arsenic exposure. Further, there was evidence of methylation-related gene regulation based on gene expression for a subset of differentially methylated loci.
  
  
  CONCLUSIONS
  We observed significant associations between arsenic exposure and gene-specific differential white blood cell DNA methylation, suggesting that epigenetic modifications may be an important pathway underlying arsenic toxicity. The specific differentially methylated loci identified may inform potential pathways for future interventions.
authors.affiliation: Department of Public Health Sciences, The University of Chicago, Chicago, Illinois, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Argos
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Farzana
authors.initials: F
authors.lastname: Jasmine
authors.forename: Lin
authors.initials: L
authors.lastname: Tong
authors.forename: Brandon L
authors.initials: BL
authors.lastname: Pierce
authors.forename: Shantanu
authors.initials: S
authors.lastname: Roy
authors.forename: Rachelle
authors.initials: R
authors.lastname: Paul-Brutus
authors.forename: Mary V
authors.initials: MV
authors.lastname: Gamble
authors.forename: Kristin N
authors.initials: KN
authors.lastname: Harper
authors.forename: Faruque
authors.initials: F
authors.lastname: Parvez
authors.forename: Mahfuzar
authors.initials: M
authors.lastname: Rahman
authors.forename: Muhammad
authors.initials: M
authors.lastname: Rakibuz-Zaman
authors.forename: Vesna
authors.initials: V
authors.lastname: Slavkovich
authors.forename: John A
authors.initials: JA
authors.lastname: Baron
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Graziano
authors.forename: Muhammad G
authors.initials: MG
authors.lastname: Kibriya
authors.forename: Habibul
authors.initials: H
authors.lastname: Ahsan
mesh_terms: D000328:Adult; D000368:Aged; D001151:Arsenic / Q000097:blood / Q000633:toxicity* / Q000652:urine; D020261:Arsenic Poisoning / Q000235:genetics; D001459:Bangladesh; D015331:Cohort Studies; D018899:CpG Islands; D004247:DNA / Q000097:blood; D019175:DNA Methylation / Q000187:drug effects*; D004785:Environmental Pollutants / Q000097:blood / Q000633:toxicity* / Q000652:urine; D044127:Epigenesis, Genetic; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged
chemical_list: D004785:Environmental Pollutants; D004247:DNA; D001151:Arsenic