Are There Sex Differences in Interactive Associations of Environmental Exposure to Lead (Pb), Mercury (Hg), and Manganese (Mn) with GST Genes (GSTP1, GSTT1, and GSTM1) in Relation to ASD in Jamaican Children?
Sex and GSTP1 genotype together influence the ASD-metal link, but the sample of girls was too small for firm conclusions.
01Research in Context
What this study did
Zwiya et al. (2023) asked whether sex changes the way lead, mercury, and manganese link to autism in Jamaican kids.
They also checked if three GST genes (GSTP1, GSTT1, GSTM1) alter that link.
The team used a case-control design, comparing children with ASD to matched peers without ASD.
What they found
Girls who carried the GSTP1 variant showed a stronger lead-autism link than boys with the same gene.
The same pattern showed up for mercury, but only in girls with the risky GSTP1 type.
Because only a small group of girls were studied, the authors call the results “tentative.”
How this fits with other research
Doughty et al. (2015) studied the same Jamaican cohort and found that high blood manganese plus the GSTP1 Ile/Ile genotype raised ASD odds four-to-six-fold. Zwiya et al. (2023) now adds sex to that story, showing the interaction is stronger in girls.
Rahaman et al. (2021) saw Bangladeshi girls with ASD have worse social play than boys, which seems to clash with the idea that girls are “less affected.” The difference is exposure: Ashiquir looked at social scores without metals, while T et al. looked at metal-gene risks, so both can be true.
Mulder et al. (2020) tested Jamaican kids again, but with PCBs and GSTM1 instead of metals and GSTP1. They also found a gene-toxin link, showing this island population often reveals GST-driven vulnerabilities.
Why it matters
If you screen Jamaican children or similar populations, record sex and GSTP1 status before you interpret metal test results. A slightly high lead level might warrant closer monitoring in a girl with the risky genotype, while the same number in a boy could mean less. Keep sample-size limits in mind: share these tentative patterns with families, but avoid firm risk statements until larger girl cohorts are studied.
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02At a glance
03Original abstract
BACKGROUND: Male preponderance is well-established in children with autism spectrum disorder (ASD). Glutathione S-transferase (GST) genes play a crucial role in suppressing oxidative stress triggered by environmental stressors. OBJECTIVE: To determine whether the association between metals and ASD differs by sex and by GST genes. METHODS: Using data from 344 pairs of sex-and age-matched cases and controls, we assessed the association of each metal with ASD or ASD severity, by applying conditional logistic regression (CLR) or general linear models (GLM). Sex was assessed as an effect modifier in separate GST genetic models. RESULTS: For Pb exposure, using a recessive model for the GSTP1 Ile105Val polymorphism, CLR revealed significant overall interaction between sex and GSTP1 (P = 0.04). However, sex-specific matched odds ratios revealed marginally lower odds of the Val/Val genotype among ASD cases than controls in females (MORfemales= 0.23 (95% CI): 0.05-1.11, P = 0.06), but not among males (MORmales= 1.18 (95% CI): 0.66-2.16, P = 0.57) in the adjusted model. GLMs for Hg exposure detected significant overall interactions in GSTP1 co-dominant and recessive genetic models. For example, the mean difference in ASD severity among children with Val/Val genotype compared to those with Ile/Ile or Ile/Val were MORfemales= -0.26 and MORmales= 1.30, respectively, in the adjusted model. CONCLUSION: The association of Pb and Hg with ASD significantly differed by sex under the GSTP1 co-dominant and recessive genetic models. Such findings reflect potential sex differences in metal detoxification mechanisms. Replication is warranted due to the limited sample size of female participants.
Research in autism spectrum disorders, 2023 · doi:10.1016/j.neuro.2014.06.007