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Res Autism Spectr Disord. 2018 Nov;55:50-63. doi: 10.1016/j.rasd.2018.08.003. Epub 2018 Sep 5.

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

Author information

1
Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.
2
Division of Clinical and Translational Sciences, Department of Internal Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.
3
Biostatistics/Epidemiology/Research Design (BERD) core, Center for Clinical and Translational Sciences (CCTS), The University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.
4
Department of Child & Adolescent Health, The University of the West Indies (UWI), Mona Campus, Kingston, Jamaica.
5
Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.
6
Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas 77054, USA.
7
Department of Basic Medical Sciences, The University of the West Indies, Mona Campus, Kingston, Jamaica.
8
Caribbean Genetics (CARIGEN),The University of the West Indies, Mona Campus, Kingston, Jamaica.
9
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA.

Abstract

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 > 12μg/L had 4.6 and 4.27 times higher odds of ASD compared to those with BMC < 12μg/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.

KEYWORDS:

Autism spectrum disorder (ASD); GSTPP; Heavy metals; Interaction; Weighted quantile sum (WQS) regression

PMID:
30930959
PMCID:
PMC6434704
[Available on 2019-11-01]
DOI:
10.1016/j.rasd.2018.08.003

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