Dataset Information

Polymorphisms in Glutathione S-Transferase (GST) Genes Modify the Effect of Exposure to Maternal Smoking Metabolites in Pregnancy and Offspring DNA Methylation.

ABSTRACT: Maternal smoking in pregnancy (MSP) affects the offspring's DNA methylation (DNAm). There is a lack of knowledge regarding individual differences in susceptibility to exposure to MSP. Glutathione S-transferase (GST) genes are involved in protection against harmful oxidants such as those found in cigarette smoke. This study aimed to test whether polymorphisms in GST genes influence the effect of MSP on offspring DNAm. Using data from the Isle of Wight birth cohort, we assessed the association of MSP and offspring DNAm in 493 mother-child dyads (251 male, 242 female) with the effect-modifying role of GST gene polymorphism (at rs506008, rs574344, rs12736389, rs3768490, rs1537234, and rs1695). MSP was assessed by levels of nicotine and its downstream metabolites (cotinine, norcotinine, and hydroxycotinine) in maternal sera. In males, associations of hydroxycotinine with DNAm at cg18473733, cg25949550, cg11647108, and cg01952185 and norcotinine with DNAm at cg09935388 were modified by GST gene polymorphisms (p-values < 0.05). In females, associations of hydroxycotinine with DNAm at cg12160087 and norcotinine with DNAm at cg18473733 were modified by GST gene polymorphisms (p-values < 0.05). Our study emphasizes the role of genetic polymorphism in GST genes in DNAm's susceptibility to MSP.

SUBMITTER: Kheirkhah Rahimabad P

PROVIDER: S-EPMC10454475 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Polymorphisms in Glutathione S-Transferase (GST) Genes Modify the Effect of Exposure to Maternal Smoking Metabolites in Pregnancy and Offspring DNA Methylation.

Kheirkhah Rahimabad Parnian P Jones A Daniel AD Zhang Hongmei H Chen Su S Jiang Yu Y Ewart Susan S Holloway John W JW Arshad Hasan H Eslamimehr Shakiba S Bruce Robert R Karmaus Wilfried W

Genes 20230818 8

Maternal smoking in pregnancy (MSP) affects the offspring's DNA methylation (DNAm). There is a lack of knowledge regarding individual differences in susceptibility to exposure to MSP. Glutathione S-transferase (GST) genes are involved in protection against harmful oxidants such as those found in cigarette smoke. This study aimed to test whether polymorphisms in GST genes influence the effect of MSP on offspring DNAm. Using data from the Isle of Wight birth cohort, we assessed the a ...[more]

PMID: 37628696

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Project description: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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Dataset Information

Polymorphisms in Glutathione S-Transferase (GST) Genes Modify the Effect of Exposure to Maternal Smoking Metabolites in Pregnancy and Offspring DNA Methylation.

Publications

Polymorphisms in Glutathione S-Transferase (<i>GST</i>) Genes Modify the Effect of Exposure to Maternal Smoking Metabolites in Pregnancy and Offspring DNA Methylation.

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Dataset Information

Polymorphisms in Glutathione S-Transferase (GST) Genes Modify the Effect of Exposure to Maternal Smoking Metabolites in Pregnancy and Offspring DNA Methylation.

Publications

Polymorphisms in Glutathione S-Transferase (&lt;i&gt;GST&lt;/i&gt;) Genes Modify the Effect of Exposure to Maternal Smoking Metabolites in Pregnancy and Offspring DNA Methylation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Polymorphisms in Glutathione S-Transferase (<i>GST</i>) Genes Modify the Effect of Exposure to Maternal Smoking Metabolites in Pregnancy and Offspring DNA Methylation.