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Association of Neuroantibodies(NAB) with Glutathione-S-Tranferase(GST) Isozyme Polymorphisms(SNP) in African-American Children with Heavy Metal Exposure
Citation:
Cichewicz, A., D. Mason, E. Hudgens, J. Gallagher, AND H. El-Fawal. Association of Neuroantibodies(NAB) with Glutathione-S-Tranferase(GST) Isozyme Polymorphisms(SNP) in African-American Children with Heavy Metal Exposure. Society of Toxicology 2015 Annual Meeting, San Diego, CA, March 22 - 26, 2015.
Impact/Purpose:
Genomic differences may play a role as determinants of heavy metal neurotoxicity, as indicated by NAb, in environmentally vulnerable populations.
Description:
Polymorphisms in GST isozymes have implications in heavy metal accumulation, neurodegeneration, and immune-mediated disease. Blood cell DNA and sera from 131 African-American children were used to determine GST Pi [rs947895 (C>A), rs17593068 (G>T), rs6591256 (A>G), rs1871042 (C>T) and rs1695 (A>G)], Mu [rs17672 (C>T), rs3815029 (G>C) and rs412543 (G>C)], and Theta [rs2266636 (present [P]>deletion[D]), rs2266637 ( [P]> [D]) and rs4630 (P >D] SNPs 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 metals (As, Cd, Cr, Cu, Fe, Hg, Mn, Pb, Se, Zn). Non-parametric analysis indicated that children with GST Pi genotypes rs1871042_TT and rs947895_AA had higher levels of As, Cd, Mn, and Pb; those with rs1695_GG had higher levels of Mn and Pb and those with rs6591256_AG had higher levels of Fe. Children with GST Mu genotypes rs17672_CC had higher levels of As and GST-Theta genotypes rs2266636_deletion;higher levels of Pb. Associations between As, Cr, Fe, Se, and Zn and IgM and IgG Nab (r=0.38-0.74; p<0.05). For Hg, Mn, and Pb, there were inverse associations (r=-.41; p<0.05) with IgM and associations (r=0.38-0.43; p<0.05) with IgG. Multiregression analysis indicated that GSTP1 and GSTT1 genotypes were the primary determinants of nail metal levels (r2=0.2; p<0.05). Additionally, the presence of metals in conjunction with select GST genotypes influenced NAb titers (r2=0.3-0.6; p<0.05). These results suggest GST Pi SNPs, in particular, determine heavy metal accumulation and NAb titers. Genomic differences may play a role as determinants of heavy metal neurotoxicity, as indicated by NAb, in environmentally vulnerable populations. This abstract does not necessarily reflect U.S. EPA policy