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 ge...notype 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.
TY - JOUR
AU - Mandić-Maravić, Vanja
AU - Corić, Vesna
AU - Mitkovic-Voncina, Marija
AU - Đorđević, Miroslav L.
AU - Savic-Radojević, Ana
AU - Ercegovac, Marko
AU - Matić, Marija
AU - Simić, Tatjana
AU - Lečić-Toševski, Dušica
AU - Tošković, Oliver
AU - Pekmezović, Tatjana
AU - Pljesa-Ercegovac, Marija
AU - Pejović-Milovančević, Milica
PY - 2019
UR - http://reff.f.bg.ac.rs/handle/123456789/2846
AB - 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.
PB - Nature Publishing Group, London
T2 - Scientific Reports
T1 - Interaction of glutathione S-transferase polymorphisms and tobacco smoking during pregnancy in susceptibility to autism spectrum disorders
VL - 9
DO - 10.1038/s41598-019-39885-w
ER -
@article{
author = "Mandić-Maravić, Vanja and Corić, Vesna and Mitkovic-Voncina, Marija and Đorđević, Miroslav L. and Savic-Radojević, Ana and Ercegovac, Marko and Matić, Marija and Simić, Tatjana and Lečić-Toševski, Dušica and Tošković, Oliver and Pekmezović, Tatjana and Pljesa-Ercegovac, Marija and Pejović-Milovančević, Milica",
year = "2019",
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.",
publisher = "Nature Publishing Group, London",
journal = "Scientific Reports",
title = "Interaction of glutathione S-transferase polymorphisms and tobacco smoking during pregnancy in susceptibility to autism spectrum disorders",
volume = "9",
doi = "10.1038/s41598-019-39885-w"
}
Mandić-Maravić, V., Corić, V., Mitkovic-Voncina, M., Đorđević, M. L., Savic-Radojević, A., Ercegovac, M., Matić, M., Simić, T., Lečić-Toševski, D., Tošković, O., Pekmezović, T., Pljesa-Ercegovac, M.,& Pejović-Milovančević, M.. (2019). Interaction of glutathione S-transferase polymorphisms and tobacco smoking during pregnancy in susceptibility to autism spectrum disorders. in Scientific Reports
Nature Publishing Group, London., 9.
https://doi.org/10.1038/s41598-019-39885-w
Mandić-Maravić V, Corić V, Mitkovic-Voncina M, Đorđević ML, Savic-Radojević A, Ercegovac M, Matić M, Simić T, Lečić-Toševski D, Tošković O, Pekmezović T, Pljesa-Ercegovac M, Pejović-Milovančević M. Interaction of glutathione S-transferase polymorphisms and tobacco smoking during pregnancy in susceptibility to autism spectrum disorders. in Scientific Reports. 2019;9.
doi:10.1038/s41598-019-39885-w .
Mandić-Maravić, Vanja, Corić, Vesna, Mitkovic-Voncina, Marija, Đorđević, Miroslav L., Savic-Radojević, Ana, Ercegovac, Marko, Matić, Marija, Simić, Tatjana, Lečić-Toševski, Dušica, Tošković, Oliver, Pekmezović, Tatjana, Pljesa-Ercegovac, Marija, Pejović-Milovančević, Milica, "Interaction of glutathione S-transferase polymorphisms and tobacco smoking during pregnancy in susceptibility to autism spectrum disorders" in Scientific Reports, 9 (2019),
https://doi.org/10.1038/s41598-019-39885-w . .
