Single nucleotide polymorphisms (SNPs) in occupational exposure assessment Public Deposited

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  • March 21, 2019
Creator
  • Jiang, Rong
    • Affiliation: Gillings School of Global Public Health, Department of Environmental Sciences and Engineering
Abstract
  • Significant individual variation exists in the systemic response to xenobiotic exposures that may be due to individual genetic differences in xenobiotic toxicokinetics, DNA-damage repair genes, host factors, and other environmentally responsive groups of genes and pathways. The source of this variation may be dependent upon single nucleotide polymorphisms (SNPs), which may result in different levels of exposure biomarkers , tissue distribution and elimination, as well as heritable differences in physiological function (e.g., blood pressure, respiratory rate). These individual genetic differences may directly or indirectly contribute to the associated health effects. Our knowledge of individual differences in toxicokinetics and systemic response to xenobiotic exposures, genetic mechanism of associated health effects, and the potential value of incorporating individual genetic variations in exposure assessment models is limited. I sought to investigate individual differences in SNPsassociated with skin naphthyl-keratin adducts (NKAs) and urine naphthol levels measured in workers exposed to jet propulsion fuel-8 (JP-8) containing naphthalene. The SNP association analysis was conducted in PLINK using candidate-gene and genome-wide analyses. I further determined the relative contributions of SNP markers and the impact of personal and workplace factors on the measured biomarker levels using multiple linear regression models. Pathway and network analyses of the genetic variants identified indicated significant associations with genes involved in the regulation of cellular and homeostasis processes that contributed to the observed level of skin NKAs. Urine naphthol levels were associated with genes involved in thyroid hormone pathways and the control of metabolism that may affect the mass movement of naphthalene and its metabolites into the cells of tissues with the capacity to metabolize and eliminate xenobiotics. I report here a method and strategy to investigate the role of individual genetic variation in the quantitative assessment of biomarker levels in small well-characterized exposed worker populations. These tools have the potential to provide biological relevance on the biomarker levels, mechanistic insight into the etiology of exposure related diseases, and identification of susceptible subpopulation with respect to exposure. Therefore, these tools will provide useful input into setting exposure limits by taking into account individual genetic variation that may relate to adverse health effects.
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  • In Copyright
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  • "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Environmental Sciences and Engineering."
Advisor
  • Nylander-French, Leena A.
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  • Chapel Hill, NC
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  • Open access
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