Prenatal and infant acetaminophen exposure, antioxidant gene polymorphisms, and childhood asthma
- PMID: 21051083
- PMCID: PMC4907348
- DOI: 10.1016/j.jaci.2010.08.047
Prenatal and infant acetaminophen exposure, antioxidant gene polymorphisms, and childhood asthma
Abstract
Background: Prenatal and infant acetaminophen exposure has been associated with an increased risk of childhood asthma phenotypes. Demonstration of biologically plausible interactions between these exposures and maternal and child antioxidant gene polymorphisms would strengthen causal inference.
Objective: To explore potential interactions between prenatal and infant acetaminophen exposure and antioxidant genotypes on childhood asthma.
Methods: In the Avon Longitudinal Study of Parents and Children, we typed a functional nuclear erythroid 2 p45-related factor 2 (Nrf2) polymorphism and glutathione S-transferase (GST) M1, T1, and P1 polymorphisms. Effects of prenatal and infant acetaminophen exposure on asthma phenotypes at 7 years were stratified by genotype in >4000 mothers and >5000 children.
Results: Risk of asthma and wheezing associated with early gestation acetaminophen exposure was increased when maternal copies of the minor T allele of Nrf2 were present (P interactions, .02 and .04, respectively). Risk of asthma associated with late gestation exposure was higher when maternal GSTT1 genotype was present rather than absent (P interaction, .006), and risk of wheezing was increased when maternal GSTM1 was present (P interaction, .04). Although acetaminophen use in infancy was associated with an increased risk of atopy, child antioxidant genotype did not modify associations between infant acetaminophen use and asthma phenotypes. However, the increased risk of asthma and wheezing associated with late gestation acetaminophen exposure in the presence of maternal GSTM1 was further enhanced when GSTM1 was also present in the child.
Conclusion: Maternal antioxidant gene polymorphisms may modify the relation between prenatal acetaminophen exposure and childhood asthma, strengthening evidence for a causal association. In contrast, relations between infant acetaminophen use and asthma and atopy were not modified by child genotype and may be confounded by pre-existing wheeze or allergy.
Copyright © 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
Conflict of interest statement
None of the authors have any conflicts of interests to declare.
Similar articles
-
Early life acetaminophen exposure, glutathione S-transferase genes, and development of adolescent asthma in a high-risk birth cohort.J Allergy Clin Immunol. 2020 Nov;146(5):1035-1044.e12. doi: 10.1016/j.jaci.2020.03.027. Epub 2020 Apr 11. J Allergy Clin Immunol. 2020. PMID: 32289338
-
Childhood asthma and use during pregnancy of acetaminophen. A critical review.Reprod Toxicol. 2010 Dec;30(4):508-19. doi: 10.1016/j.reprotox.2010.09.005. Epub 2010 Oct 8. Reprod Toxicol. 2010. PMID: 20933592 Review.
-
Maternal Nrf2 and gluthathione-S-transferase polymorphisms do not modify associations of prenatal tobacco smoke exposure with asthma and lung function in school-aged children.Thorax. 2010 Oct;65(10):897-902. doi: 10.1136/thx.2009.125856. Epub 2010 Aug 30. Thorax. 2010. PMID: 20805158
-
Glutathione-S-transferase genes and asthma phenotypes: a Human Genome Epidemiology (HuGE) systematic review and meta-analysis including unpublished data.Int J Epidemiol. 2010 Apr;39(2):539-62. doi: 10.1093/ije/dyp337. Epub 2009 Dec 23. Int J Epidemiol. 2010. PMID: 20032267 Free PMC article. Review.
-
Prenatal acetaminophen exposure and risk of wheeze at age 5 years in an urban low-income cohort.Thorax. 2010 Feb;65(2):118-23. doi: 10.1136/thx.2009.121459. Epub 2009 Oct 22. Thorax. 2010. PMID: 19850963 Free PMC article.
Cited by
-
Photocatalytic degradation of paracetamol by semiconductor oxides under UV and sunlight illumination.Turk J Chem. 2022 Jul 19;46(6):1866-1874. doi: 10.55730/1300-0527.3486. eCollection 2022. Turk J Chem. 2022. PMID: 37621336 Free PMC article.
-
Racing against time: leveraging preclinical models to understand pulmonary susceptibility to perinatal acetaminophen exposures.Am J Physiol Lung Cell Mol Physiol. 2022 Jul 1;323(1):L1-L13. doi: 10.1152/ajplung.00080.2022. Epub 2022 May 3. Am J Physiol Lung Cell Mol Physiol. 2022. PMID: 35503238 Free PMC article. Review.
-
Association of prenatal acetaminophen use and acetaminophen metabolites with DNA methylation of newborns: analysis of two consecutive generations of the Isle of Wight birth cohort.Environ Epigenet. 2022 Feb 2;8(1):dvac002. doi: 10.1093/eep/dvac002. eCollection 2022. Environ Epigenet. 2022. PMID: 35317219 Free PMC article.
-
Long-Term Safety of Prenatal and Neonatal Exposure to Paracetamol: A Systematic Review.Int J Environ Res Public Health. 2022 Feb 14;19(4):2128. doi: 10.3390/ijerph19042128. Int J Environ Res Public Health. 2022. PMID: 35206317 Free PMC article. Review.
-
Genetic Susceptibility to Drug Teratogenicity: A Systematic Literature Review.Front Genet. 2021 Apr 27;12:645555. doi: 10.3389/fgene.2021.645555. eCollection 2021. Front Genet. 2021. PMID: 33981330 Free PMC article.
References
-
- Newson RB, Shaheen SO, Chinn S, Burney PGJ. Paracetamol sales and atopic disease in children and adults: an ecological analysis. Eur Respir J. 2000;16:817–823. - PubMed
-
- Etminan M, Sadatsafavi M, Jafari S, Doyle-Waters M, Aminzadeh K, FitzGerald JM. Acetaminophen Use and the Risk of Asthma in Children and Adults. Chest. 2009;136:1316–1323. - PubMed
-
- Beasley R, Clayton T, Crane J, von Mutius E, Lai CK, Montefort S, et al. Association between paracetamol use in infancy and childhood, and risk of asthma, rhinoconjunctivitis, and eczema in children aged 6-7 years: analysis from Phase Three of the ISAAC programme. The Lancet. 2008;372:1039–1048. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Medical
Research Materials
Miscellaneous