Interaction between manganese and GSTP1 in relation to autism spectrum disorder while controlling for exposure to mixture of lead, mercury, arsenic, and cadmium

Background: We previously reported a significant interactive association between polymorphisms of GSTP1 and blood manganese concentrations (BMC) with autism spectrum disorder (ASD) in Jamaican children. In this paper, we investigate the same interactive association with ASD while adjusting for the mixture of four metals (lead, mercury, cadmium, and arsenic). Method: We used data from 163 case-control pairs of children 2–8 years of age from our autism project in Jamaica, in which we collected blood for heavy metals analysis at enrollment. To minimize potential multicollinearity between concentrations of the four metals, we generated a mixture index using generalized weighted quantile sum regression, which was used in conditional logistic regression models to control for the four metals while assessing the interactive association between GSTP1 and BMC with ASD. Results: Similar to the findings we reported previously, we found that in co-dominant and dominant models for GSTP1, among children with the Ile/Ile genotype, those with BMC ≥ 12 μg/L had 4.6 and 4.27 times higher odds of ASD compared to those with BMC < 12 μg/L (adjusted Matched Odds Ratio (MOR) = 4.6, 95% CI: 1.21–17.42 and adjusted MOR = 4.27, 95% CI: 1.15–15.85, respectively). In the co-dominant model, for children with the Ile/Val and Val/Val genotypes, the adjusted MORs were 1.26 (95% CI: 0.32, 5.01) and 0.26 (95% CI: 0.05, 1.42), respectively. Conclusions: After adjusting for the mixture of four metals, the interactive association of BMC and GSTP1 with ASD remained significant with similar magnitude of associations. Results should be interpreted cautiously.