AUTHOR=Mandic-Maravic Vanja , Mitkovic-Voncina Marija , Pljesa-Ercegovac Marija , Savic-Radojevic Ana , Djordjevic Miroslav , Ercegovac Marko , Pekmezovic Tatjana , Simic Tatjana , Pejovic-Milovancevic Milica 

TITLE=Glutathione S-Transferase Polymorphisms and Clinical Characteristics in Autism Spectrum Disorders

JOURNAL=Frontiers in Psychiatry

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2021.672389

DOI=10.3389/fpsyt.2021.672389

ISSN=1664-0640

ABSTRACT=<p><bold>Background:</bold> Autism spectrum disorders (ASD) are a heterogeneous group of developmental disorders, with different levels of symptoms, functioning, and comorbidities. Recent findings suggested that oxidative stress and genetic variability in glutathione S-transferases (GSTs) might increase the risk of ASD development. We aimed to determine whether GST polymorphisms influence the severity of symptoms as well as the cognitive and adaptive abilities in children with ASD.</p><p><bold>Methods:</bold> The sample included 113 ASD cases. All participants were genotyped for GSTA1, GSTM1, GSTT1, and GSTP1 polymorphisms. The clinical characteristics were determined with Autism Diagnostic Interview-Revised (ADI-R) in all of the participants. In non-verbal participants, we explored the adaptive functioning using the Vineland Adaptive Behavior Scale II, while in verbal participants, we used the Wechsler Abbreviated Scale of Intelligence (WASI).</p><p><bold>Results:</bold> It was shown that the <italic>GSTA1</italic><sup>*</sup><italic>CC</italic> genotype was a predictor of a lower non-verbal communication impairment as well as of a lower chance of having seizures during life. <italic>GSTM1-active</italic> genotype predicted a higher adaptive functioning. The predictive effect of <italic>GSTA1, GSTM1</italic>, and <italic>GSTT1</italic> genotype was moderated by exposure during pregnancy (maternal smoking and medication). The <italic>GSTP1</italic><sup>*</sup><italic>IleIle</italic> genotype was significantly associated to a better cognitive functioning in children with ASD.</p><p><bold>Conclusion:</bold> Besides the complex gene-environment interaction for the specific risk of developing ASD, there is also a possible complexity of interactions between genetic and environmental factors influencing the level of symptoms and impairment in people with ASD. Detoxification and antioxidant enzymes, such as GSTA1, might contribute to the core of this complexity.</p>