Detoxification Role of Metabolic Glutathione S-Transferase (GST) Genes in Blood Lead Concentrations of Jamaican Children with and without Autism Spectrum Disorder

Abstract

Glutathione S-transferases (GST) are involved in the detoxification of exogenous chemicals including lead (Pb). Using data from 344 pairs of autism spectrum disorder (ASD) cases and age- and sex-matched typically developing (TD) controls (2–8 years old) from Jamaica, we investigated the interaction between three GST genes and ASD status as determinants of blood Pb concentrations (BPbCs). We found that ASD cases had lower geometric mean BPbCs than TD children (1.74 vs. 2.27 µg/dL, p < 0.01). Using a co-dominant genetic model, ASD cases with the Ile/Val genotype for the GSTP1 Ile105Val polymorphism had lower GM BPbCs than TD controls, after adjusting for a known interaction between GSTP1 and GSTT1, child’s parish, socioeconomic status, consumption of lettuce, fried plantains, and canned fish (Ile/Val: 1.78 vs. 2.13 µg/dL, p = 0.03). Similarly, among carriers of the I/I or I/D (I*) genotype for GSTT1 and GSTM1, ASD cases had lower adjusted GM BPbCs than TD controls (GSTT1 I*: 1.61 vs. 1.91 µg/dL, p = 0.01; GSTM1 I*: 1.71 vs. 2.04 µg/dL, p = 0.01). Our findings suggest that genetic polymorphisms in GST genes may influence detoxification of Pb by the enzymes they encode in Jamaican children with and without ASD.

Machine Learning Assisted Discovery of Interactions between Pesticides, Phthalates, Phenols, and Trace Elements in Child Neurodevelopment

“…The concept of “interaction” has been construed in many ways through different scientific fields . For example, in epidemiological studies, interactions are usually reported through association estimates of their effect sizes or inclusion probabilities. − Though estimating associations is essential, most methods do not provide any mechanistic or biological insight, possibly because the reported interactions are of particular functional forms (for example, multiplication of exposures) rather than representing their collective activities beyond certain concentration thresholds . Further, after applying certain dimension reductions, most interactions are reported between sets of reduced exposures, limiting interpretability.…”

Machine learning assisted discovery of synergistic interactions between environmental pesticides, phthalates, phenols, and trace elements in child neurodevelopment

“…The concept of "interaction" has been construed in many ways through different scientific fields 21 . For example, in current epidemiological studies, interactions are usually reported through association estimates of their effect sizes or inclusion probabilities [22][23][24][25][26][27][28][29][30][31][32][33] . Though estimating associations is essential, most methods do not provide any mechanistic or biological insight, possibly because the reported interactions are of particular functional forms (for example, multiplication of exposures) rather than representing their collective activities beyond certain concentration thresholds 34 .…”