Interaction between GSTT1 and GSTP1 allele variants as a risk modulating-factor for autism spectrum disorders

Rahbar, Mohammad Hossein; Samms‐Vaughan, Maureen; Ma, Jianchao; Bressler, Jan; Loveland, Katherine A.; Hessabi, Manouchehr; Dickerson, Aisha S.; Grove, Megan L.; Shakespeare-Pellington, Sydonnie; Beecher, Compton; McLaughlin, Wayne; Boerwinkle, Eric

doi:10.1016/j.rasd.2014.12.008

Cited by 22 publications

(26 citation statements)

References 65 publications

(99 reference statements)

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“…Over the years, many studies have attempted to elucidate triggering genetic factors in the development of ASD 4 , however, so far only several studies evaluated the possible association between GST polymorphisms, as independent factor (or in conjunction with environmental factors), and susceptibility to ASD 10,11,16,17 . Cytosolic GST family catalyzes the conjugation of electrophilic compounds, including products of oxidative stress, with GSH 9 .…”

Section: Discussionmentioning

confidence: 99%

“…Multiple lines of evidence which suggested that oxidative stress could represent the basis for the observed association between genetic, immunological and environmental factors underlying autism 13,19–21 , also suggested the role of glutathione transferases in ASD development, in particular when taking into account the important antioxidant role of GSTs 11,17,22 .…”

Section: Introductionmentioning

confidence: 99%

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

Mandic-Maravic

Ćorić

Mitkovic-Voncina

et al. 2019

Sci Rep

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Mandic-Maravic

Ćorić

Mitkovic-Voncina

et al. 2019

Sci Rep

View full text Add to dashboard Cite

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“…For typically developing controls, we ruled out symptoms of ASD using the Social Communication Questionnaire (SCQ) Lifetime form (Rutter, Bailey, & Lord, 2003) with a cut-off score of 6, which is one standard deviation above the mean SCQ score for typically developing children (Mulligan, Richardson, Anney, & Gill, 2009). Details on the recruitment and assessment procedures of this study have been reported previously (Rahbar et al, 2012a; Rahbar et al, 2012b; Rahbar et al, 2013; Rahbar et al, 2014a; Rahbar et al, 2014b; Rahbar et al, 2014c; Rahbar et al, 2015). …”

Section: Methodsmentioning

confidence: 99%

“…If the child had difficulty in spitting 2 mL of saliva, then the Oragene Discover OGR-575 for Assisted Collection with sponges was used (DNA Genotek). Saliva and whole blood samples (plasma, buffy coat, and red blood cell aliquots) were shipped from UWI to UTHealth for genetic analyses and details regarding DNA isolation and genotyping of GSTT1, GSTM1 , and GSTP1 were reported previously (Rahbar et al, 2014c; Rahbar et al, 2015). …”

Section: Methodsmentioning

confidence: 99%

Synergic effect of GSTP1 and blood manganese concentrations in Autism Spectrum Disorder

Rahbar

Samms‐Vaughan

et al. 2015

Research in Autism Spectrum Disorders

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We used data from 100 age- and sex-matched case-control pairs (age 2–8 years) from Jamaica to investigate whether there is an interaction between glutathione-S-transferase (GST) genes and blood manganese concentrations (BMC) in relation to Autism Spectrum Disorder (ASD). Our findings, indicate that among children who had the Ile/Ile genotype for GST pi 1 (GSTP1), those with BMC ≥ 12µg/L had about 4 times higher odds of ASD than those with BMC < 12µg/L, (P=0.03) under a co-dominant genetic model. After adjusting for potential confounders, among the subgroup of children with genotype Ile/Ile, those with BMC ≥ 12µg/L had about six times higher odds of ASD than those with BMC < 12µg/L, (P=0.04). The results were similar when a recessive genetic model was used. These findings suggest a possible synergic effect of BMC and GSTP1 in ASD. Since our analysis included a variety of genetic models and was not adjusted for multiple testing, replication in other populations is warranted.

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“…Recent findings from our Jamaican study of children with ASD and TD children revealed that the relationship between GSTP1 and blood arsenic concentrations varied by ASD status (TD or ASD) in an interactive model [42] In addition, we identified a significant gene-gene interaction between GSTP1 and GSTT1 in relation to ASD, where there was a significantly higher odds of ASD for children who were heterozygous for the GSTP1 Ile105Val polymorphism and had the GSTT1 null genotype (Matched Odds Ratio (MOR) = 2.97, 95% CI (1.09, 8.01), p = 0.03) [43]. Furthermore, we found a significant gene-environment interaction between GSTP1 and blood manganese concentrations (BMC) indicating that among children who had the Ile/Ile genotype for GSTP1 , those with BMC ≥ 12 µg/L had about four times higher odds of ASD than those with BMC < 12 µg/L ( p = 0.03) [44].…”

Section: Introductionmentioning

confidence: 99%

Role of Metabolic Genes in Blood Aluminum Concentrations of Jamaican Children with and without Autism Spectrum Disorder

Rahbar

Samms‐Vaughan

Pitcher

et al. 2016

IJERPH

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Aluminum is a neurotoxic metal with known health effects in animals and humans. Glutathione-S-transferase (GST) genes and enzymes play a major role in detoxification of several heavy metals. Besides a direct relationship with oxidative stress; aluminum decreases GST enzyme activities. Using data from 116 Jamaican children; age 2–8 years; with Autism Spectrum Disorder (ASD) and 116 sex- and age-matched typically developing (TD) children; we investigated the association of polymorphisms in three GST genes (GSTP1; GSTM1; and GSTT1) with mean blood aluminum concentrations in children with and without ASD. Using log-transformed blood aluminum concentration as the dependent variable in a linear regression model; we assessed the additive and interactive effects of ASD status and polymorphisms in the three aforementioned GST genes in relation to blood aluminum concentrations. Although none of the additive effects were statistically significant (all p > 0.16); we observed a marginally significant interaction between GSTP1 Ile105Val (rs1695) and ASD status (p = 0.07); even after controlling for parental education level and consumption of avocado; root vegetables; and tuna (canned fish). Our findings indicate a significantly lower (p < 0.03) adjusted geometric mean blood aluminum concentration for TD children who had the Val/Val genotype (14.57 µg/L); compared with those with Ile/Ile or Ile/Val genotypes who had an adjusted geometric mean of 23.75 µg/L. However; this difference was not statistically significant among the ASD cases (p = 0.76). Our findings indicate that ASD status may be a potential effect modifier when assessing the association between GSTP1 rs1695 and blood aluminum concentrations among Jamaican children. These findings require replication in other populations.

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Interaction between GSTT1 and GSTP1 allele variants as a risk modulating-factor for autism spectrum disorders

Cited by 22 publications

References 65 publications

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

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

Synergic effect of GSTP1 and blood manganese concentrations in Autism Spectrum Disorder

Role of Metabolic Genes in Blood Aluminum Concentrations of Jamaican Children with and without Autism Spectrum Disorder

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