Role of Glutathione-S-Transferase M1 (GSTM1) and T1 (GSTT1) Genes on Aluminum Concentration and Oxidative Markers among Autistic Children

Abstract

Autism Spectrum Disorder (ASD) is considered a multifaceted neurodevelopmental disorder. The last two decades showed an increase in its prevalence until reached about 1 in 54 children. Autistic symptoms may be exacerbated when the interaction of the genetic and the environmental risk factors occur, suggesting that gene-environment interaction could be a mechanism underlying the aetiology of ASD. Aluminium is a known neurotoxic metal that has known health effects in humans. Glutathione-S-transferase (GST) genes and their enzymes play a major role in the detoxification of many toxic metals. Data were collected from 76 children aged 2-8 years diagnosed with ASD and 30 sex and age matched healthy children. The aim of this study was to investigate the association of polymorphisms in the two GST genes (GSTM1 and GSTT1) with mean aluminium concentrations (as, gene-environment interaction) and oxidative status markers (GST enzyme, malondialdehyde and nitric oxide) among the studied groups. The study started at December 2019 and last for one year at the clinics of National Research Centre, Egypt. The results of this study showed that the null GSTM1 and GSTT1 genotype is the most common type in ASD and that genotype may predispose ASD children to decreased antioxidant status (GST enzyme activity) which in term lead to mal detoxification of aluminium. There is marked increase in aluminium concentrations in hair of ASD children and oxidative markers (increase in MDA and NO) leading to oxidative damage that may play an important role in children autistic status. The study recommends adding antioxidant supplements to daily diet of ASD children to improve their antioxidant status and in term improving management of patients with autism spectrum disorders. Further studies are needed to describe other GST gene polymorphisms.

Interactions between Environmental Factors and Glutathione S-Transferase (GST) Genes with Respect to Detectable Blood Aluminum Concentrations in Jamaican Children

“…Moreover, several findings suggested that the differential susceptibility to heavy metals can be explained by the polymorphisms of GST genes, for instance, null alleles of GSTT1 and GSTM1 were associated with a deficiency of enzymatic activity which was related to decreased detoxification and increased oxidative stress [ 43 , 47 ]. According to a recent study in Egypt, children with null GSTM1 and GSTT1 genotypes had a significantly lower level of GST activity compared to other combinations of genotypes, suggesting a poor aluminum detoxification ability [ 48 ]. All of these reports indicate that genetic variation can provide an explanation for differences in Al concentrations in a population.…”

Antioxidants as a Potential Therapy for Reduction of Oxidative Stress in Autistic Children

“…Some studies have shown that Glutathione S-Transferases (GSTs) enzymes have a very essential function in antioxidant protection mechanisms via performing the detoxification of xenobiotics and inactivation of endogenous oxidative stress products [13]. In addition to, our recent study observed that autistic children have reduced glutathione activity, and increased oxidative stress [9]. This open the possibility for novel treatments aiming at planning dietary antioxidant interventions in children with ASD.…”

“…7 (2022) recommended via 49% of physicians as a supplementation for children with autism [6]. Some studies have depicted the role of Al in autism spectrum disorder [7][8][9], due to its poor detoxification. The oxidative stress become worse and it is found to be associated with autism severity that significantly lead to ASD progression [8,9].…”

“…Some studies have depicted the role of Al in autism spectrum disorder [7][8][9], due to its poor detoxification. The oxidative stress become worse and it is found to be associated with autism severity that significantly lead to ASD progression [8,9]. Oxidative stress causes mechanisms that are important in inducing ASD.…”

“…Oxidative stress causes mechanisms that are important in inducing ASD. In addition to the genegene interactions and gene-environment interaction which may also potentiate oxidative stress in ASD children [9][10][11]. Oxidative stress is a situation that takes place due to the imbalance between synthesis of reactive oxygen/nitrogen species (ROS/RNS) and the organism's potential to reduce their deleterious effect via anti-oxidative protection systems.…”