Synergic effect of GSTP1 and blood manganese concentrations in Autism Spectrum Disorder

• We studied the synergistic effect of blood manganese levels (Mn) and GSTP1 in ASD.
• Odds of ASD was higher in children with Mn ≥ 12 μg/L and GSTP1 Ile/Ile genotype.
• Children with Mn ≥ 12 μg/L and GSTP1 Ile/Ile genotype had 4 times higher odds of ASD.
• Children with Mn ≥ 12 μg/L and Ile/Ile genotype had 6 times higher adjusted odds of ASD.

We used data from 100 age- and sex-matched case-control pairs (age 2–8 years) from Jamaica to investigate whether there is an interaction between glutathione-S-transferase (GST) genes and blood manganese concentrations (BMC) in relation to Autism Spectrum Disorder (ASD). Our findings, indicate that among children who had the Ile/Ile genotype for GST pi 1 (GSTP1), those with BMC ≥ 12 μg/L had about 4 times higher odds of ASD than those with BMC < 12 μg/L, (P = 0.03) under a co-dominant genetic model. After adjusting for potential confounders, among the subgroup of children with genotype Ile/Ile, those with BMC ≥ 12 μg/L had about six times higher odds of ASD than those with BMC < 12 μg/L, (P = 0.04). The results were similar when a recessive genetic model was used. These findings suggest a possible synergic effect of BMC and GSTP1 in ASD. Since our analysis included a variety of genetic models and was not adjusted for multiple testing, replication in other populations is warranted.