The interactions among organophosphate pesticide exposure, oxidative stress and genetic polymorphisms of dopamine receptor D4 increase the risk of attention deficit/hyperactivity disorder in children
Abstract
Objective The aim of this study was to clarify the association between organophosphate pesticides (OPs) and attention-deficit/hyperactivity disorder (ADHD) related to oxidative stress and genetic polymorphisms.Methods This case-control study enrolled 93 children with ADHD and 112 control children in north Taiwan. Six dialkyl phosphate (DAP) metabolites of OPs and oxidative stress biomarkers were analyzed. Polymorphisms of the dopamine receptor D4 gene (DRD4) were identified.Results Children with ADHD had significantly higher dimethylphosphate (DMP, 236.69nmol/g cre. vs. 186.84nmol/g cre., p value = 0.01) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA, 28.95µg/g cre. vs. 16.55µg/g cre., p value<0.01) concentrations than control children. Children who carried DRD4 GA/AA genotypes (rs752306) were less likely than those who carried the DRD4 GG genotype to have ADHD (odds ratio [OR]: 0.45, 95% CI: 0.24-0.84). The estimated value of the AP (attributable proportion due to interaction) was 0.59 (95% CI: 0.13-1.05), indicating that 59% of ADHD cases in DMP-exposed children with the DRD4 GG genotype were due to the gene-environment interaction. After adjustment for other covariates, children who carried the DRD4 GG genotype, had been exposed to high DMP levels (more than the median), and had high HNE-MA levels had a significantly increased risk for developing ADHD (OR = 11.74, 95% CI: 2.12-65.04).Conclusion This study indicated a gene-environment interaction in the risk of ADHD in children. The association between DMP and ADHD in children might relate to the mechanism of lipid peroxidation. Dose-response relationships and the combined effects of OPs, oxidative stress, and genetic polymorphism on ADHD should not be neglected.
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DRD4 has been reported to significantly interact with high stress level during pregnancy and some chemical toxins, such as dimethyl phosphate, in children with ADHD.
“DRD4 has been reported to significantly interact with high stress level during pregnancy and some chemical toxins, e.g., dimethyl phosphate, in children with ADHD (Grizenko et al., 2012; Chang et al., 2018).”
From A Review of Heterogeneity in Attention Deficit/Hyperactivity Disorder (ADHD) (2019) · cites this paper as Chang et al., 2018
Organophosphate pesticides, polychlorinated biphenyls, and lead may damage the neural systems implicated in ADHD.
“In particular, organophosphate pesticides, polychlorinated biphenyls, and lead may damage the neural systems implicated in ADHD (Nigg, 2008; Chang et al., 2018).”
From A Review of Heterogeneity in Attention Deficit/Hyperactivity Disorder (ADHD) (2019) · cites this paper as Chang et al., 2018
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- Authors
- Chang, C.-H., Yu, C.-J., Du, J.-C., Chiou, H.-C., Chen, H.-C., Yang, W., Chung, M.-Y., Chen, Y.-S., Hwang, B., Mao, I.-F., & Chen, M.-L.
- Affiliations
- National Yang Ming University (TW)
- Taipei City Hospital (TW)
- Taipei Municipal YangMing Hospital (TW)
- National Taiwan University (TW)
- Taipei Veterans General Hospital (TW)
- Chung Shan Medical University (TW)
- Corresponding author
- Chen, Hsin-Chang
- Chen, Ying-Sheue
- Chen, Mei-Lien
- Venue
- Environmental Research
- Publisher
- Elsevier BV
- Published
- 2018-01
- Volume
- 160
- Pages
- 339-346
- ISSN
- 0013-9351 (ISSN-L)
- OpenAlex
- W2766198297
- Cited by
- 54
- References
- 73
- Citations by year
- 2026: 7 · 2025: 3 · 2024: 7 · 2023: 5 · 2022: 6 · 2021: 7 · 2020: 11 · 2019: 5 · 2018: 3
- FWCI
- 5.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Environmental Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Science and Technology of the Republic of China (MOST 103-2319-B-010-001, 10301-62-004)
- Department of Health, Taipei City Government
- Topics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Pesticide Exposure and Toxicity
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Paraoxonase enzyme and polymorphisms
- Keywords
- organophosphorus pesticides, attention deficit hyperactivity disorder, children, oxidative stress, dopamine D4 receptor, dimethyl phosphate, dialkyl phosphate metabolites, lipid peroxidation, gene-environment interaction, pesticide exposure
- MeSH terms
- Adolescent, Attention Deficit Disorder with Hyperactivity, Child, Child, Preschool, Female, Humans, Male, Pesticides, Organophosphates, Lipid Peroxidation, Case-Control Studies, Oxidative Stress, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Receptors, Dopamine D4, Gene-Environment Interaction
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