26969
Interaction between Manganese and GSTP1 in Relation to Autism Spectrum Disorder While Controlling for Exposure to Mixture of Lead, Mercury, Arsenic, and Cadmium
Poster Presentation
Saturday, May 12, 2018: 11:30 AM-1:30 PM
Hall Grote Zaal (de Doelen ICC Rotterdam)
M. H. Rahbar1, M. E. Samms-Vaughan2, M. Lee1, M. A. Bach3, J. Bressler4, M. Hessabi3, M. L. Grove5, S. Pellington2, C. Coore Desai6, J. A. T. Reece6, K. A. Loveland7 and E. Boerwinkle8, (1)Division of Clinical and Translational Sciences, Department of Internal Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, (2)Department of Child & Adolescent Health, The University of the West Indies, Mona Campus, Kingston, Jamaica, (3)Biostatistics/Epidemiology/Research Design (BERD) core, Center for Clinical and Translational Sciences (CCTS), The University of Texas Health Science Center at Houston, Houston, TX, (4)Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, (5)Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, (6)Department of Child & Adolescent Health, The University of the West Indies, Kingston, Jamaica, (7)Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, (8)Department of Epidemiology, Human Genetics, and Environmental Sciences, Human Genetics Center, University of Texas School of Public Health at Houston, Houston, TX
Background: Humans are regularly exposed to a combination of environmental chemicals, including heavy metals and metalloids, which have potentially neurotoxic effects. Although neurotoxic effects are known for some individual metals, there is limited published information on the combined neurotoxicity of heavy metals. It is possible that even when individual metals are below their ecotoxicological benchmark levels, interactions among a mixture of metals could result in more severe health effects. Several metals are known to induce oxidative stress, which has previously been linked with autism spectrum disorder (ASD). Glutathione S-transferase (GST) enzymes, encoded by genes in the
GST gene family, play a protective role against oxidative stress. We have previously reported a significant interaction between polymorphisms of
GSTP1 and blood manganese concentrations (BMC) in relation to ASD in Jamaican children. However, we did not control for the potential confounding effect of the mixture of other metals.
Objectives: To investigate whether the interaction between GSTP1 and blood manganese concentrations in relation to ASD will remain statistically significant after controlling for exposure to a mixture of four other metals, including lead, mercury, cadmium, and arsenic.
Methods: We used data from 163 pairs of Jamaican children 2-8 years of age enrolled in the Epidemiological Research on Autism in Jamaica (ERAJ) or ERAJ- Phase II matched case-control studies. To minimize any potential multicollinearity between blood concentrations of lead, mercury, arsenic, and cadmium, we used generalized weighted quantile sum (WQS) regression. Then, we used conditional logistic regression models to assess the interaction effect between GSTP1 and manganese in relation to ASD, controlling for the weighted score of the four metals (i.e., WQS) and other potential confounders. In this analysis, we considered the co-dominant genetic model previously used to assess the interaction of GSTP1 genotype and BMC in relation to ASD.
Results: We found that the interaction between GSTP1 and blood manganese concentration remained significant after adjusting for the mixture of lead, mercury, cadmium, and arsenic and additional potential confounders. Using the co-dominant model for GSTP1, results indicated that among children with the Ile/Ile genotype, those with BMC ≥ 12µg/L had 4.6 times higher odds of ASD compared to those with BMC < 12µg/L (adjusted Matched Odds Ratio (MOR) = 4.6, 95% CI: 1.21 – 17.42).
Conclusions: Our previously published finding that GSTP1 genotype may be an effect modifier for the association between binary blood manganese concentrations and ASD in Jamaica remained statistically significant after adjusting for the mixture effect of lead, mercury, cadmium, and arsenic. It is important to consider mixtures of environmental exposures when investigating their associations with ASD since exposures do not occur in isolation.
