Abstract
Background: Autism spectrum disorders (ASD) are complex psychiatric disorders, with gene environment interaction being in the basis of their etiology. The association of perinatal complications and ASD is well established. Recent findings suggested that oxidative stress and polymorphism in genes encoding antioxidant enzymes might be involved in the development of ASD. Glutathione transferases (GSTs) have an important role in the antioxidant defense system. We aimed to establish whether the predictive effects of prenatal and perinatal complications (as possible oxidative stress inducers) on ASD risk are dependent on GST polymorphisms. Methods: The study included 113 ASD cases and 114 age- and sex group-matched healthy controls. All participants were genotyped for GSTA1, GSTM1, GSTT1, and GSTP1 polymorphisms. The questionnaire regarding prenatal and perinatal risk factors and complications was administered for all the subjects in the study. Results: The evaluated perinatal complications as a group significantly increased the risk of ASD [odds ratio (OR) = 9.415; p = 0.000], as well as individual perinatal complications, such as prematurity (OR = 11.42; p = 0.001), neonatal jaundice (OR = 8.774; p = 0.000), respiratory distress syndrome (OR = 4.835; p = 0.047), and the use of any medication during pregnancy (OR = 2.413; p = 0.03). In logistic regression model, adding GST genotypes did not modify the significant effects found for prematurity and neonatal jaundice as risk factors in ASD. However, there was a significant interaction of GST genotype with medication use during pregnancy and the use of tocolytics during pregnancy, which was predictive of ASD risk only in carriers of GSTM1-null, as opposed to carriers of GSTM1-active genotype. Conclusion: Specific perinatal complications may be significant risk factors for ASD. GSTM1 genotype may serve as a moderator of the effect of some prenatal factors on the risk of ASD such as using medication during pregnancy. It may be speculated that different oxidative stress-related genetic and environmental factors could lead to development of ASD. Apart from etiological mechanisms, possible therapeutic implications in ASD are also discussed.
Highlights
The increasing prevalence of autism spectrum disorder (ASD) has led to an increase in interest for environmental factors and their potential influence [1]
There were no differences in maternal age (p = 0.465) or paternal age (p = 0.159) as well
Having any perinatal complication raised the risk of ASD 9.415 times (p = 0.000; odds ratios (OR) = 9.415; confidence intervals (CIs): 4.870–18.203)
Summary
The increasing prevalence of autism spectrum disorder (ASD) has led to an increase in interest for environmental factors and their potential influence [1]. Multiple studies explored the effect of prenatal and perinatal factors on the risk of ASD. They explored various factors, using different criteria, and getting different results [5]. Maternal age was found to be significant in several large studies, [6, 7], while the most recent study showed a different finding—the risk for ASD might increase if the mother is younger [8]. It is argued that maternal age might have a direct effect on ASD risk—possibly by epigenetic changes [9], and might increase the risk for perinatal complications in general [10]. We aimed to establish whether the predictive effects of prenatal and perinatal complications (as possible oxidative stress inducers) on ASD risk are dependent on GST polymorphisms
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