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Neuroantibodies (NAB) in African-American Children with Heavy Metal Exposures are Associated with Cytokine and Human Leukocyte Antigen (HLA) Polymorphisms (SNP)
Citation:
Dougherty, K., A. Cichewicz, E. Hudgens, J. Gallagher, AND H. El-Fawal. Neuroantibodies (NAB) in African-American Children with Heavy Metal Exposures are Associated with Cytokine and Human Leukocyte Antigen (HLA) Polymorphisms (SNP). SOT 2015, San Diego, CA, March 22 - 26, 2015.
Impact/Purpose:
The ability to monitor neurodegeneration non-invasively would facilitate the monitoring of health effects in environmentally and genomically vulnerable populations.
Description:
Polymorphisms in cytokine and HLA genes are associated with allergies, autoimmunity and neurodegeneration (ND). Samples from 131 African-American children (71 males; 60 females) in the Mechanistic Indicators of Childhood Asthma (MICA) study were used to determine SNPs of IL-4, IL-13, TNFα, HLADQB1 and HLADRB1 by PCR for associations with NAb, IgM and IgG, against neurofilaments (NF-L, NF-M and NF-H), GFAP and myelin basic protein (MBP) and nail metal levels (As, Cd, Cr, Cu, Fe, Hg, Mn, Pb, Se and Zn). Overall, with the exception of IL-4 SNPs and Hg, (rs2243267 G>C; rs2070874 C>T; rs2243290 C>A; rs2243270 G>A; rs734244 G>A) and HLA-DRB1 SNPs and Fe (rs9269701 G>A; rs9269743 A>G), metal levels did not differ by SNP genotype. For all IL-4 heterozygous SNP genotypes, Hg was higher (p<0.001) than either homozygous genotype. For HLADRB1, the homozygous GG and AA genotypes, Fe levels were higher (p<0.01). Non-parametric analysis indicated significant differences in NAb titers based on cytokine SNPs. For IL-13 rs20541 (C>T), the heterozygous genotype had higher levels of anti-NF-M, IgM, NF-H and MBP, IgG. For IL-4 rs2070874 (C>T) and rs734244 (G>T) anti-NF-H (IgM) were higher (p<0.05) than heterozygous genotypes, while anti-GFAP (IgG) in rs2243267 (G>C) and rs2243290 (C>A) were higher (p<0.05) for genotypes GG and CC, respectively. Significant differences (p<0.005-0.05) in 2 or more of anti-NF, GFAP and MBP, IgM or IgG titers, were observed for all TNFα SNPs [rs1800629 G>A; rs3093662 A>G; rs3093664 A>G; rs3093665 A>C; rs3093668 G>C] with titers being higher for heterozygous genotypes. Anti-NF-L, IgM, was higher (p<0.05) for HLADRB1 rs9269743_AA or _AG compared to the null genotype. Multiregression modeling indicated As, Cd, Hg, Mn, Pb, HLADRB1, TNFα and IL-4 were major determinants of NAb titers (r2=0.6; p<0.05). These results suggest that levels of NAb are influenced by SNPs in proinflammatory or neuroprotective cytokine genes. This autoimmune response indicative of ND, secondary to environmental insult, may be modified by HLA SNPs. The ability to monitor ND non-invasively would facilitate the monitoring of health effects in environmentally and genomically vulnerable populations. This abstract does not necessarily reflect USEPA policy.