4.3 Article

Associations of Metabolic Genes (GSTT1, GSTP1, GSTM1) and Blood Mercury Concentrations Differ in Jamaican Children with and without Autism Spectrum Disorder

Publisher

MDPI
DOI: 10.3390/ijerph18041377

Keywords

autism spectrum disorder (ASD); blood mercury concentrations; glutathione S-transferase (GST) genes; seafood consumption; interaction; Jamaica

Funding

  1. National Institute of Environmental Health Sciences (NIEHS) [R01ES022165]
  2. Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  3. National Institutes of Health Fogarty International Center (NIH-FIC) [R21HD057808]
  4. Biostatistics/Epidemiology/Research Design (BERD) component of the Center for Clinical and Translational Sciences (CCTS)
  5. NIH Centers for Translational Science Award (NIH CTSA) grant [UL1 RR024148]
  6. National Center for Advancing Translational Sciences (NCATS) [UL1 TR000371, UL1TR003167]

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The study revealed significant interactions between GSTP1 and ASD status in relation to blood Hg concentrations, suggesting different levels of BHC based on genotype in ASD cases and typically developing controls. Further replication studies in other populations are needed to confirm the role of GSTP1 in detoxification of Hg.
We investigated interactive roles of three metabolic glutathione S-transferase (GST) genes (GSTP1, GSTT1, and GSTM1) and autism spectrum disorder (ASD) status in relation to blood Hg concentrations (BHC) of Jamaican children. We used data from 266 children (2-8 years) with ASD and their 1:1 age- and sex-matched typically developing (TD) controls. After adjusting General Linear Models for child's age, socioeconomic status, consumption of leafy vegetables, fried plantain, canned fish, and the interaction between GSTP1 and GSTT1, we found significant interactions between GSTP1 and ASD status in relation to BHC either in a co-dominant or dominant genetic model for GSTP1(P < 0.001, P = 0.007, respectively). In the co-dominant model for the Ile105Val GSTP1 polymorphism, geometric mean (GM) BHC in ASD cases with genotype Ile/Ile were significantly higher than in cases with the Ile/Val genotype (0.73 vs. 0.48 mu g/L, P = 0.01). In contrast, in TD controls with the Ile/Val genotype GM BHC were significantly higher than in those with the Ile/Ile genotype (0.72 vs. 0.49 mu g/L, P = 0.03) or the Val/Val genotype (0.72 vs. 0.51 mu g/L, P = 0.04). Although our findings are consistent with the role of GSTP1 in detoxification of Hg, replication in other populations is warranted.

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