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Neuroantibodies (NAB) in African-American Children: Associations with Gender, Glutathione-S-Transferase (GST)Pi Polymorphisms (SNP) and Heavy Metals
Cichewicz, A., E. Hudgens, J. Gallagher, AND H. El-Fawal. Neuroantibodies (NAB) in African-American Children: Associations with Gender, Glutathione-S-Transferase (GST)Pi Polymorphisms (SNP) and Heavy Metals. Presented at Society of Toxicology Meeting, Phoenix, AZ, March 24 - 27, 2014.
CONTACT (NAME ONLY): Hassan El-Fawal Abstract Details PRESENTATION TYPE: Platform or Poster CURRENT CATEGORY: Neurodegenerative Disease | Biomarkers | Neurotoxicity, Metals KEYWORDS: Autoantibodies, Glutathione-S-Transferase, DATE/TIME LAST MODIFIED: DATE/TIME SUBMITTED: Abstract TITLE: NEUROANTIBODIES (NAB) IN AFRICAN-AMERICAN CHILDREN: ASSOCIATIONS WITH GENDER, GLUTATHIONE-S-TRANSFERASE (GST) Pi POLYMORPHISMS (SNP) AND HEAVY METALS AUTHORS (LAST NAME, FIRST NAME): Cichewicz, Allie1; Hudgens, Edward E2; Gallagher, Jane E2; El-Fawal, Hassan A.1 SPONSOR NAME: None INSTITUTIONS (ALL): 1. Neurotoxicology Laboratory, Albany College of Pharmacy and Health Sciences, Albany, NY, United States. 2. Environmental Public Health Division, NHEERL, US EPA, Research Triangle Park, NC, United States. ABSTRACT BODY: Polymorphisms in GST are implicated in immune-mediated disease, heavy metal accumulation and neurodegeneration. Blood cell DNA/serum samples from 131 African-American children (9-12 years old, 71 males; 60 females) in the Mechanistic Indicators of Childhood Asthma (MICA) study were used to determine GSTPi SNPs [rs947895 (C>A), rs6591256 (A>G), rs1695 (A>G), rs1871042 (C>T) and rs17593068 (G>T)] by PCR for associations with NAb, IgM and IgG, against neurofilaments (NF-L, NF-M and NF-H), glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP) and nail heavy metal levels (As, Cd, Cr, Cu, Fe, Hg, Mn, Pb, Se and Zn). Overall, non-parametric analysis indicated significant associations (r=0.23; p<0.05) between anti-NF-H and anti-MBP with As and Pb, while anti-GFAP was also associated with Pb levels. Heavy metal levels did not differ on stratification by gender. However, females had higher levels of anti-NF-L and anti-NF-H, IgM, and anti-NF-M, IgG (p<0.05). In females only, there were significant (p<0.01-0.05) positive associations of anti-NF-H, GFAP and MBP, IgG, with As, Cr, Fe, Mn, Pb and Se, and with Cd and Cu for anti-NF-H and GFAP. Genotype stratifications revealed significantly higher levels of As, Cd, Mn and Pb in children with the rs947895_AA and rs1871042_TT genotypes. Higher Mn and Pb levels were found in children with the rs1695_GG genotype. Stronger associations between NAb and several metals were observed in these genotypes with higher metal levels, These results suggest that NAb, may be useful for detection of nervous system involvement in environmentally and genomically vulnerable populations and that females may be at greater risk as established by the prevalence of autoimmunity in this gender. This abstract does not necessarily reflect U.S. EPA policy.
The Mechanistic Indicator Of childhood Asthma study has provide valuable data for identifying exposure-related autoantibody titers that may indicate neurotoxic without overt toxicity. This is necessary for adequately estimating the human risk to environmental toxic exposures and for identifying the toxic factors responsible for the adverse health effects in susceptible human populations, like children.
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Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB
ENVIRONMENTAL PUBLIC HEALTH DIVISION