Role of Metabolic Genes in Blood Aluminum Concentrations of Jamaican Children with and without Autism Spectrum Disorder.
Aluminum is a neurotoxic metal with known health effects in animals and humans. Glutathione-S-transferase (GST) genes and enzymes play a major role in detoxification of several heavy metals. Besides a direct relationship with oxidative stress; aluminum decreases GST enzyme activities. Using data from 116 Jamaican children; age 2-8 years; with Autism Spectrum Disorder (ASD) and 116 sex- and age-matched typically developing (TD) children; we investigated the association of polymorphisms in three GST genes (GSTP1;GSTM1; andGSTT1) with mean blood aluminum concentrations in children with and without ASD. Using log-transformed blood aluminum concentration as the dependent variable in a linear regression model; we assessed the additive and interactive effects of ASD status and polymorphisms in the three aforementioned GST genes in relation to blood aluminum concentrations. Although none of the additive effects were statistically significant (allp> 0.16); we observed a marginally significant interaction betweenGSTP1Ile105Val (rs1695) and ASD status (p= 0.07); even after controlling for parental education level and consumption of avocado; root vegetables; and tuna (canned fish). Our findings indicate a significantly lower (p< 0.03) adjusted geometric mean blood aluminum concentration for TD children who had the Val/Val genotype (14.57 µg/L); compared with those with Ile/Ile or Ile/Val genotypes who had an adjusted geometric mean of 23.75 µg/L. However; this difference was not statistically significant among the ASD cases (p= 0.76). Our findings indicate that ASD status may be a potential effect modifier when assessing the association betweenGSTP1rs1695 and blood aluminum concentrations among Jamaican children. These findings require replication in other populations.
Division of Epidemiology, Human Genetics, and Environmental Sciences (EHGES), University of Texas School of Public Health at Houston, Houston, TX 77030, USA. Mohammad.H.Rahbar@uth.tmc.edu.|Division of Clinical and Translational Sciences, Department of Internal Medicine, University of Texas McGovern Medical School at Houston, Houston, TX 77030, USA. Mohammad.H.Rahbar@uth.tmc.edu.|Center for Clinical and Translational Sciences (CCTS), University of Texas Health Science Center at Houston, Houston, TX 77030, USA. Mohammad.H.Rahbar@uth.tmc.edu.
Mohammad H
MH
Rahbar
Department of Child & Adolescent Health, The University of the West Indies (UWI), Mona Campus, Kingston 7, Jamaica. msammsvaughan@gmail.com.
Maureen
M
Samms-Vaughan
Center for Clinical and Translational Sciences (CCTS), University of Texas Health Science Center at Houston, Houston, TX 77030, USA. Meagan.R.Pitcher@uth.tmc.edu.
Meagan R
MR
Pitcher
Division of Epidemiology, Human Genetics, and Environmental Sciences (EHGES), University of Texas School of Public Health at Houston, Houston, TX 77030, USA. Jan.Bressler@uth.tmc.edu.|Human Genetics Center, University of Texas School of Public Health at Houston, Houston, TX 77030, USA. Jan.Bressler@uth.tmc.edu.
Jan
J
Bressler
Center for Clinical and Translational Sciences (CCTS), University of Texas Health Science Center at Houston, Houston, TX 77030, USA. Manouchehr.Hessabi@uth.tmc.edu.
Manouchehr
M
Hessabi
Department of Psychiatry and Behavioral Sciences, University of Texas McGovern Medical School at Houston, Houston, TX 77054, USA. Katherine.A.Loveland@uth.tmc.edu.
Katherine A
KA
Loveland
Center for Clinical and Translational Sciences (CCTS), University of Texas Health Science Center at Houston, Houston, TX 77030, USA. Mackinsey.A.Christian@uth.tmc.edu.
MacKinsey A
MA
Christian
Human Genetics Center, University of Texas School of Public Health at Houston, Houston, TX 77030, USA. Megan.L.Grove@uth.tmc.edu.
Megan L
ML
Grove
Department of Child & Adolescent Health, The University of the West Indies (UWI), Mona Campus, Kingston 7, Jamaica. sydonniesp@gmail.com.
Sydonnie
S
Shakespeare-Pellington
Department of Basic Medical Sciences, The University of the West Indies, Mona Campus, Kingston 7, Jamaica. compton.beecher@uwimona.edu.jm.
Compton
C
Beecher
Department of Basic Medical Sciences, The University of the West Indies, Mona Campus, Kingston 7, Jamaica. wayne.mclaughlin@uwimona.edu.jm.|Caribbean Genetics (CARIGEN), The University of the West Indies, Mona Campus, Kingston 7, Jamaica. wayne.mclaughlin@uwimona.edu.jm.
Wayne
W
McLaughlin
Division of Epidemiology, Human Genetics, and Environmental Sciences (EHGES), University of Texas School of Public Health at Houston, Houston, TX 77030, USA. Eric.Boerwinkle@uth.tmc.edu.|Human Genetics Center, University of Texas School of Public Health at Houston, Houston, TX 77030, USA. Eric.Boerwinkle@uth.tmc.edu.
Eric
E
Boerwinkle
D000535:Aluminum / Q000097:blood*; D000067877:Autism Spectrum Disorder / Q000209:etiology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004785:Environmental Pollutants / Q000097:blood*; D005260:Female; D051549:Glutathione S-Transferase pi / Q000235:genetics* / Q000378:metabolism; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007563:Jamaica; D008297:Male; D011110:Polymorphism, Genetic
D000535:Aluminum; D004785:Environmental Pollutants; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human
Autism Spectrum Disorder (ASD); aluminum; detoxification; glutathione S-transferase (GST) genes; interactions