Prenatal Exposure to Arsenic and Cadmium Impacts Infectious Disease-Related Genes within the Glucocorticoid Receptor Signal Transduction Pathway

Details

• Alternative Title:
  Int J Mol Sci
• Personal Author:
  Rager, Julia E. ; Yosim, Andrew ; Fry, Rebecca C.
• Description:
  There is increasing evidence that environmental agents mediate susceptibility to infectious disease. Studies support the impact of prenatal/early life exposure to the environmental metals inorganic arsenic (iAs) and cadmium (Cd) on increased risk for susceptibility to infection. The specific biological mechanisms that underlie such exposure-mediated effects remain understudied. This research aimed to identify key genes/signal transduction pathways that associate prenatal exposure to these toxic metals with changes in infectious disease susceptibility using a Comparative Genomic Enrichment Method (CGEM). Using CGEM an infectious disease gene (IDG) database was developed comprising 1085 genes with known roles in viral, bacterial, and parasitic disease pathways. Subsequently, datasets collected from human pregnancy cohorts exposed to iAs or Cd were examined in relationship to the IDGs, specifically focusing on data representing epigenetic modifications (5-methyl cytosine), genomic perturbations (mRNA expression), and proteomic shifts (protein expression). A set of 82 infection and exposure-related genes was identified and found to be enriched for their role in the glucocorticoid receptor signal transduction pathway. Given their common identification across numerous human cohorts and their known toxicological role in disease, the identified genes within the glucocorticoid signal transduction pathway may underlie altered infectious disease susceptibility associated with prenatal exposures to the toxic metals iAs and Cd in humans.
• Subjects:
  Arsenic Article Cadmium Cohort Studies Communicable Diseases Environmental Toxicant Epigenome Female Gene Regulatory Networks Genome Glucocorticoid Receptor Humans Infectious Disease In Utero Pathway Pregnancy Prenatal Exposure Delayed Effects Receptors, Glucocorticoid Reproducibility Of Results Risk Factors Signal Transduction Toxicogenetics

  More +
• Source:
  Int J Mol Sci. 2014; 15(12):22374-22391.
• Pubmed ID:
  25479081
• Pubmed Central ID:
  PMC4284714
• Document Type:
  Journal Article
• Funding:
  2T42 OH-008673/OH/NIOSH CDC HHS/United States ; P30 ES010126/ES/NIEHS NIH HHS/United States ; P30-ES010126/ES/NIEHS NIH HHS/United States ; P42 ES005948/ES/NIEHS NIH HHS/United States ; P42-ES005948/ES/NIEHS NIH HHS/United States ; R01-ES019315/ES/NIEHS NIH HHS/United States
• Volume:
  15
• Issue:
  12
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:c902a9d18d6f8e443dcac09e5b486770bfbc4dc65bad495b7eab6ccf8cb582f1
• Download URL:
  https://stacks.cdc.gov/view/cdc/27524/cdc_27524_DS1.pdf
• File Type:
  [PDF - 1.23 MB ]