TY - JOUR
T1 - 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
AU - Chang, Chia Huang
AU - Yu, Ching Jung
AU - Du, Jung Chieh
AU - Chiou, Hsien Chih
AU - Chen, Hsin Chang
AU - Yang, Winnie
AU - Chung, Ming Yi
AU - Chen, Ying Sheue
AU - Hwang, Betau
AU - Mao, I. Fang
AU - Chen, Mei Lien
N1 - Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2018/1
Y1 - 2018/1
N2 - 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, 236.69 nmol/g cre. vs. 186.84 nmol/g cre., p value = 0.01) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA, 28.95 µg/g cre. vs. 16.55 µg/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.
AB - 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, 236.69 nmol/g cre. vs. 186.84 nmol/g cre., p value = 0.01) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA, 28.95 µg/g cre. vs. 16.55 µg/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.
KW - Additive interaction
KW - Attention deficit/hyperactivity disorder
KW - Dopamine receptor D4 gene
KW - Organophosphate pesticides
KW - Oxidative stress
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U2 - 10.1016/j.envres.2017.10.011
DO - 10.1016/j.envres.2017.10.011
M3 - Article
C2 - 29054088
AN - SCOPUS:85031497965
SN - 0013-9351
VL - 160
SP - 339
EP - 346
JO - Environmental Research
JF - Environmental Research
ER -