title: Bisphenol A-associated epigenomic changes in prepubescent girls: a cross-sectional study in Gharbiah, Egypt.
abstract: BACKGROUND
  There is now compelling evidence that epigenetic modifications link adult disease susceptibility to environmental exposures during specific life stages, including pre-pubertal development. Animal studies indicate that bisphenol A (BPA), the monomer used in epoxy resins and polycarbonate plastics, may impact health through epigenetic mechanisms, and epidemiological data associate BPA levels with metabolic disorders, behavior changes, and reproductive effects. Thus, we conducted an environmental epidemiology study of BPA exposure and CpG methylation in pre-adolescent girls from Gharbiah, Egypt hypothesizing that methylation profiles exhibit exposure-dependent trends.
  
  
  METHODS
  Urinary concentrations of total (free plus conjugated) species of BPA in spot samples were quantified for 60 girls aged 10 to 13. Genome-wide CpG methylation was concurrently measured in bisulfite-converted saliva DNA using the Infinium HumanMethylation27 BeadChip (N = 46). CpG sites from four candidate genes were validated via quantitative bisulfite pyrosequencing.
  
  
  RESULTS
  CpG methylation varied widely among girls, and higher urinary BPA concentrations were generally associated with less genomic methylation. Based on pathway analyses, genes exhibiting reduced methylation with increasing urinary BPA were involved in immune function, transport activity, metabolism, and caspase activity. In particular, hypomethylation of CpG targets on chromosome X was associated with higher urinary BPA. Using the Comparative Toxicogenomics Database, we identified a number of candidate genes in our sample that previously have been associated with BPA-related expression change.
  
  
  CONCLUSIONS
  These data indicate that BPA may affect human health through specific epigenomic modification of genes in relevant pathways. Thus, epigenetic epidemiology holds promise for the identification of biomarkers from previous exposures and the development of epigenetic-based diagnostic strategies.
authors.affiliation: Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Jung H
authors.initials: JH
authors.lastname: Kim
authors.forename: Laura S
authors.initials: LS
authors.lastname: Rozek
authors.forename: Amr S
authors.initials: AS
authors.lastname: Soliman
authors.forename: Maureen A
authors.initials: MA
authors.lastname: Sartor
authors.forename: Ahmed
authors.initials: A
authors.lastname: Hablas
authors.forename: Ibrahim A
authors.initials: IA
authors.lastname: Seifeldin
authors.forename: Justin A
authors.initials: JA
authors.lastname: Colacino
authors.forename: Caren
authors.initials: C
authors.lastname: Weinhouse
authors.forename: Muna S
authors.initials: MS
authors.lastname: Nahar
authors.forename: Dana C
authors.initials: DC
authors.lastname: Dolinoy
mesh_terms: D000293:Adolescent; D001559:Benzhydryl Compounds / Q000633:toxicity* / Q000652:urine; D002648:Child; D016000:Cluster Analysis; D003430:Cross-Sectional Studies; D003596:Cytosine / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects*; D004534:Egypt; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000633:toxicity* / Q000652:urine; D044127:Epigenesis, Genetic / Q000187:drug effects*; D005260:Female; D055106:Genome-Wide Association Study; D006147:Guanine / Q000378:metabolism; D006801:Humans; D016015:Logistic Models; D010636:Phenols / Q000633:toxicity* / Q000652:urine; D016133:Polymerase Chain Reaction; D043922:Toxicogenetics; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D003596:Cytosine; D004785:Environmental Pollutants; D006147:Guanine; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds