Abstract
Autism spectrum disorders (ASD) are a group of complex psychiatric disorders, with a proposed gene-environment interaction in their etiology. One mechanism that could explain both the genetic and environmental component is oxidative stress. The aim of our study was to investigate the potential role of common polymorphisms in genes for glutathione transferase A1, M1, T1 and P1 in susceptibility to ASD. We also aimed to explore the possible oxidative stress - specific gene-environment interaction, regarding GST polymorphisms, maternal smoking tobacco during pregnancy (TSDP) and the risk of ASD. This case-control study included 113 children with ASD and 114 age and sex-matched controls. The diagnosis was made based on ICD-10 criteria and verified by Autism Diagnostic Interview – Revised (ADI-R). We investigated GSTA1, GSTM1, GSTP1 and GSTT1 genotypes and explored their individual and combined effects in individuals with ASD. Individual effect of GST genotypes was shown for GSTM1 active genotype decreasing the risk of ASD (OR = 0.554, 95%CI: 0.313–0.983, p = 0.044), and for GSTA1 CC genotype, increasing susceptibility to ASD (OR = 4.132, 95%CI: 1.219–14.012, p = 0.023); the significance was lost when genotype-genotype interactions were added into the logistic regression model. The combination of GSTM1 active and GSTT1 active genotype decreased the risk of ASD (OR = 0.126, 95%CI: 0.029–0.547, p = 0.006), as well as combination of GSTT1 active and GSTP1 llelle (OR = 0.170, 95%CI: 0.029–0.992, p = 0.049). Increased risk of ASD was observed if combination of GSTM1 active and GSTP1 llelle was present (OR = 11.088, 95%CI: 1.745–70.456, p = 0.011). The effect of TSDP was not significant for the risk of ASD, neither individually, nor in interaction with specific GST genotypes. Specific combination of GST genotypes might be associated with susceptibility to ASD, while it appears that maternal smoking during pregnancy does not increase the risk of ASD.
Highlights
Autism spectrum disorders (ASD) represent a group of disorders which include symptoms such as impairment of social interactions, impairment of communication and restricted interests and repetitive behavior[1]
The present study investigated polymorphic expression in four classes of glutathione S-transferases (GSTA1, GSTM1, GSTT1 and GSTP1) in individuals with ASD, as well as their possible gene-gene and gene-environment interaction underlying this disorder
The results of this study showed that the GSTM1 null and GSTA1 CC genotypes were significantly more frequent in patients with ASD
Summary
Autism spectrum disorders (ASD) represent a group of disorders which include symptoms such as impairment of social interactions, impairment of communication (both verbal and nonverbal) and restricted interests and repetitive behavior[1]. Www.nature.com/scientificreports that the period of susceptibility to environmental factors in ASD, might be the prenatal and perinatal period of development[5]. The explanation for the assumption lies in the fact that GSTs or, more precisely, genetic polymorphism observed in almost all classes of GST superfamily, might increase the individual susceptibility to environmental factors associated with ASD12, and to oxidative stress[13]. Glutathione transferases, as part of gene-environment interaction in development of ASD, were mentioned a decade ago by Williams et al (2007) who noted higher risk of ASD in children of women with GSTP1 Ile/Val genotype, further suggesting that risk factors during pregnancy might result in higher risk of ASD in later life[10]
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