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Interaction of glutathione S-transferase polymorphisms and tobacco smoking during pregnancy in susceptibility to autism spectrum disorders.

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.

SUBMITTER: Mandic-Maravic V

PROVIDER: S-EPMC6397281 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Interaction of glutathione S-transferase polymorphisms and tobacco smoking during pregnancy in susceptibility to autism spectrum disorders.

Mandic-Maravic Vanja V Coric Vesna V Mitkovic-Voncina Marija M Djordjevic Miroslav M Savic-Radojevic Ana A Ercegovac Marko M Matic Marija M Simic Tatjana T Lecic-Tosevski Dusica D Toskovic Oliver O Pekmezovic Tatjana T Pljesa-Ercegovac Marija M Pejovic-Milovancevic Milica M

Scientific reports 20190301 1

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, ...[more]

PMID: 30824761

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Project description:Given inconsistent evidence on preconception or prenatal tobacco use and offspring autism spectrum disorder (ASD), this study assessed associations of maternal smoking with ASD and ASD-related traits. Among 72 cohorts in the Environmental Influences on Child Health Outcomes consortium, 11 had ASD diagnosis and prenatal tobaccosmoking (n = 8648). and 7 had Social Responsiveness Scale (SRS) scores of ASD traits (n = 2399). Cohorts had diagnoses alone (6), traits alone (2), or both (5). Diagnoses drew from parent/caregiver report, review of records, or standardized instruments. Regression models estimated smoking-related odds ratios (ORs) for diagnoses and standardized mean differences for SRS scores. Cohort-specific ORs were meta-analyzed. Overall, maternal smoking was unassociated with child ASD (adjusted OR, 1.08; 95% confidence interval [CI], 0.72-1.61). However, heterogeneity across studies was strong: preterm cohorts showed reduced ASD risk for exposed children. After excluding preterm cohorts (biased by restrictions on causal intermediate and exposure opportunity) and small cohorts (very few ASD cases in either smoking category), the adjusted OR for ASD from maternal smoking was 1.44 (95% CI, 1.02-2.03). Children of smoking (versus non-smoking) mothers had more ASD traits (SRS T-score + 2.37 points, 95% CI, 0.73-4.01 points), with results homogeneous across cohorts. Maternal preconception/prenatal smoking was consistently associated with quantitative ASD traits and modestly associated with ASD diagnosis among sufficiently powered United States cohorts of non-preterm children. Limitations resulting from self-reported smoking and unmeasured confounders preclude definitive conclusions. Nevertheless, counseling on potential and known risks to the child from maternal smoking is warranted for pregnant women and pregnancy planners. LAY SUMMARY: Evidence on the association between maternal prenatal smoking and the child's risk for autism spectrum disorder has been conflicting, with some studies reporting harmful effects, and others finding reduced risks. Our analysis of children in the ECHO consortium found that maternal prenatal tobacco smoking is consistently associated with an increase in autism-related symptoms in the general population and modestly associated with elevated risk for a diagnosis of autism spectrum disorder when looking at a combined analysis from multiple studies that each included both pre- and full-term births. However, this study is not proof of a causal connection. Future studies to clarify the role of smoking in autism-like behaviors or autism diagnoses should collect more reliable data on smoking and measure other exposures or lifestyle factors that might have confounded our results.

Dataset Information

Interaction of glutathione S-transferase polymorphisms and tobacco smoking during pregnancy in susceptibility to autism spectrum disorders.

Publications

Interaction of glutathione S-transferase polymorphisms and tobacco smoking during pregnancy in susceptibility to autism spectrum disorders.

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