TY - JOUR
T1 - Bisphenol A-associated epigenomic changes in prepubescent girls
T2 - A cross-sectional study in Gharbiah, Egypt
AU - Kim, Jung H.
AU - Rozek, Laura S.
AU - Soliman, Amr S.
AU - Sartor, Maureen A.
AU - Hablas, Ahmed
AU - Seifeldin, Ibrahim A.
AU - Colacino, Justin A.
AU - Weinhouse, Caren
AU - Nahar, Muna S.
AU - Dolinoy, Dana C.
N1 - Funding Information:
This work was supported by the University of Michigan NIEHS Center of excellence P30 ES017885 and by NIH grant ES017524. Support for CW, JAC, and MSN was provided by NIEHS Institutional Training Grant T32 ES007062. Support for JAC was also provided by NHGRI Institutional Training Grant T32 HG00040. We would like to acknowledge Dr. Antonia Calafat and her team at the National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA for their part in the analysis of BPA concentrations. We would also like to acknowledge Ms. Stacy Endres for her effort in part of the data collection in Egypt and the Cancer Epidemiology Education in Special Population Program Grant R25 CA112383. The authors have no conflicts of interest and declare no competing financial interests.
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - Bead array
KW - Bisphenol A
KW - DNA methylation
KW - Egypt
KW - Epigenetics
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U2 - 10.1186/1476-069X-12-33
DO - 10.1186/1476-069X-12-33
M3 - Article
C2 - 23590724
AN - SCOPUS:84877833286
SN - 1476-069X
VL - 12
JO - Environmental Health: A Global Access Science Source
JF - Environmental Health: A Global Access Science Source
IS - 1
M1 - 33
ER -