Neuroantibody Titer Associations with Glutathione-S-Transferase and Human Leukocyte Antigen Polymorphisms in African-American Children with Heavy Metal Exposures

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Issue Date
2014
Authors
Cichewicz, Allie '14
Degree
MS in Pharmaceutical Sciences
Advisor
El-Fawal, Hassan
Committee Members
Mousa, Shaker
Mason, Darius
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Abstract
Recent years have witnessed an increased interest in gene-environment interactions and the establishment of links between environmental chemicals, allergies, and neurodegenerative and autoimmune diseases. The impetus for this interest is multifactorial, deriving from epidemiological studies of greater risk associated with genomic differences in vulnerable populations and a failure to identify the etiological factors for what are considered sporadic diseases. Towards this end, the Environmental Protection Agency's (EPA) Mechanistic Indicators of Childhood Asthma (MICA) study was undertaken to investigate markers of allergic asthma and single nucleotide polymorphisms (SNPs) of key genes reported to increase risk of allergic asthma, as well as heavy metal exposures. The present study determined titers of autoantibodies against nervous system-specific proteins (NAb) in African-American children as an ancillary study to MICA. Non-parametric analyses indicated that SNPs in genes encoding glutathione-S-transferase (GST) Pi and Theta detoxifying isozymes were primarily involved in heavy metal accumulation, with males having higher metal levels. SNPs in GST, as well as HLA, genes influenced NAb titers against the neurofilament triplet proteins. Females had higher NAb titers than males. Multiregression modeling of transformed data indicated that NAb titers were primarily determined by GSTP1 homozygous and heterozygous genotypes, GSTM1 homozygous genotypes and the presence of GST Theta genes. Heavy metal exposure also enhanced these genetic influences. These results suggest a role for genomic differences as determinants of heavy metal neurotoxicity, as indicated by NAb, in environmentally vulnerable populations with differences in sex also being a factor.
Citation
Cichewicz A. Neuroantibody titer associations with glutathione-s-transferase and human leukocyte antigen polymorphisms in African-American children with heavy metal exposures [thesis]. Ann Arbor (MI): Proquest LLC; 2014. 135 p.
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