Prenatal exposure to arsenic and cadmium impacts infectious disease-related genes within the glucocorticoid receptor signal transduction pathway
Autor: | Andrew Yosim, Julia E. Rager, Rebecca C. Fry |
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Rok vydání: | 2014 |
Předmět: |
epigenome
Disease 010501 environmental sciences 01 natural sciences Toxicogenetics lcsh:Chemistry Cohort Studies Glucocorticoid receptor Pregnancy Risk Factors glucocorticoid receptor Gene Regulatory Networks lcsh:QH301-705.5 Spectroscopy Genetics 0303 health sciences environmental toxicant General Medicine 3. Good health Computer Science Applications Prenatal Exposure Delayed Effects Female Signal transduction Glucocorticoid signal transduction medicine.drug cadmium infectious disease Biology Communicable Diseases in utero Catalysis Article Inorganic Chemistry 03 medical and health sciences Receptors Glucocorticoid medicine Humans Epigenetics Physical and Theoretical Chemistry Molecular Biology Gene genome 030304 developmental biology 0105 earth and related environmental sciences pathway Organic Chemistry arsenic Reproducibility of Results Epigenome lcsh:Biology (General) lcsh:QD1-999 Infectious disease (medical specialty) Immunology |
Zdroj: | International Journal of Molecular Sciences Volume 15 Issue 12 Pages 22374-22391 International Journal of Molecular Sciences, Vol 15, Iss 12, Pp 22374-22391 (2014) |
ISSN: | 1422-0067 |
Popis: | 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. |
Databáze: | OpenAIRE |
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