Polymorphisms in glutathione S-transferase (GST) genes modify the effect of exposure to maternal smoking metabolites in pregnancy and offspring DNA methylation
Polymorphisms in glutathione S-transferase (GST) genes modify the effect of exposure to maternal smoking metabolites in pregnancy and offspring DNA methylation
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.
DNA methylation, genetic polymorphism, glutathione S-transferase, pregnancy, smoking
1644
Kheirkhah Rahimabad, Parnian
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Jones, A. Daniel
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Zhang, Hongmei
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Chen, Su
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Jiang, Yu
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Ewart, Susan
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Holloway, John W.
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Arshad, Syed
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Eslamimehr, Shakiba
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Bruce, Robert
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Karmaus, Wilfried
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18 August 2023
Kheirkhah Rahimabad, Parnian
fa337379-ff1a-4c4e-849d-b849c634a41e
Jones, A. Daniel
373d5a88-2568-4684-99a9-ed1076179d1b
Zhang, Hongmei
9f774048-54d6-4321-a252-3887b2c76db0
Chen, Su
e492aa31-d7fc-422e-bc73-8ab92275db77
Jiang, Yu
4fa0a27b-8c06-4988-832a-8f5fb3a3f1ec
Ewart, Susan
28667421-3cf7-43d7-b1c3-ca27564938f7
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Arshad, Syed
917e246d-2e60-472f-8d30-94b01ef28958
Eslamimehr, Shakiba
11fb403f-2c15-4499-bf16-97eb849bc13d
Bruce, Robert
7d20e6c9-41c2-4e18-9b33-02710fa276f6
Karmaus, Wilfried
281d0e53-6b5d-4d38-9732-3981b07cd853
Kheirkhah Rahimabad, Parnian, Jones, A. Daniel, Zhang, Hongmei, Chen, Su, Jiang, Yu, Ewart, Susan, Holloway, John W., Arshad, Syed, Eslamimehr, Shakiba, Bruce, Robert and Karmaus, Wilfried
(2023)
Polymorphisms in glutathione S-transferase (GST) genes modify the effect of exposure to maternal smoking metabolites in pregnancy and offspring DNA methylation.
Genes, 14 (8), , [1644].
(doi:10.3390/genes14081644).
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.
Text
genes-14-01644
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Accepted/In Press date: 15 August 2023
Published date: 18 August 2023
Additional Information:
Funding Information:
The funding for this research was provided by the National Institute of Allergy and Infectious Diseases [R01 AI091905] and the National Heart, Lung, and Blood Institute [R01 HL132321], awarded to W.K. A.D.J. acknowledges support from Michigan AgBioResearch, which is funded by the USDA National Institute of Food and Agriculture, under the Hatch project number MICL02474.
Publisher Copyright:
© 2023 by the authors.
Keywords:
DNA methylation, genetic polymorphism, glutathione S-transferase, pregnancy, smoking
Identifiers
Local EPrints ID: 481546
URI: http://eprints.soton.ac.uk/id/eprint/481546
ISSN: 2073-4425
PURE UUID: ce933fb6-39c3-4853-8210-64d8a2bf535e
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Date deposited: 01 Sep 2023 16:53
Last modified: 10 Aug 2024 01:35
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Contributors
Author:
Parnian Kheirkhah Rahimabad
Author:
A. Daniel Jones
Author:
Hongmei Zhang
Author:
Su Chen
Author:
Yu Jiang
Author:
Susan Ewart
Author:
Shakiba Eslamimehr
Author:
Robert Bruce
Author:
Wilfried Karmaus
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