TY - JOUR
T1 - The associations among organophosphate pesticide exposure, oxidative stress, and genetic polymorphisms of paraoxonases in children with attention deficit/hyperactivity disorder
AU - Chang, Chia Huang
AU - Yu, Ching Jung
AU - Du, Jung Chieh
AU - Chiou, Hsien Chih
AU - Hou, Jia Woei
AU - Yang, Winnie
AU - Chen, Chian Feng
AU - Chen, Hsin Chang
AU - Chen, Ying Sheue
AU - Hwang, Betau
AU - Chen, Mei Lien
N1 - Funding Information:
This study was financially supported by the Ministry of Science and Technology of the Republic of China (MOST107-2314-B-010-051-MY2) and the Department of Health, Taipei City Government. We acknowledge the High-throughput Genome Analysis Core Facility of National Core Facility Program for Biotechnology, Taiwan, for providing SNP genotyping support. This manuscript has been edited by American Journal Experts.
Funding Information:
This study was financially supported by the Ministry of Science and Technology of the Republic of China ( MOST107-2314-B-010-051-MY2 ) and the Department of Health, Taipei City Government . We acknowledge the High-throughput Genome Analysis Core Facility of National Core Facility Program for Biotechnology, Taiwan, for providing SNP genotyping support. This manuscript has been edited by American Journal Experts.
Publisher Copyright:
© 2021 Elsevier B.V.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/6/15
Y1 - 2021/6/15
N2 - This study will help to clarify the relationship between organophosphate pesticides (OPs) and attention deficit/hyperactivity disorder (ADHD) related to oxidative stress and paraoxonases (PON) polymorphisms to further characterize the gene-environment interaction. This case-control study enrolled 85 children with ADHD and 96 control subjects. Urinary OP levels were analyzed by using gas chromatography–mass spectrometry (GC–MS). Oxidative stress biomarkers, such as 8-hydroxy-2-deoxyguanosine (8-OHdG), 8-nitroguanine (8-NO2-Gua), 8-iso-prostaglandin F2α (8-iso-PGF2α), and 4-hydroxy-2-nonenoic acid-mercapturic acid (HNE-MA), were analyzed by using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (S) were calculated to evaluate the additive interactions between OP exposure and PON genetic polymorphism on ADHD. A causal mediation analysis was conducted to clarify the mediation effects of oxidative stress due to OP exposure on ADHD. Children with ADHD had significantly higher DMP (238.95 nmol/g cre. vs. 164.83 nmol/g cre., p value = 0.01) and HNE-MA (30.75 μg/g cre. vs. 18.41 μg/g cre., p value<0.01) concentrations than control children. Children who carried the PON1 GG genotype (rs705379) had low urinary DMP levels, and the level increased with increasing numbers of allele variants. The risk for developing ADHD reached 2.06-fold (OR = 2.06, 95% CI:1.23–3.44) and 1.43-fold (OR = 1.45, 95% CI:1.04–2.03) when the DMP and HNE-MA levels increased by 1 natural log of the concentration, respectively. The estimated AP value was 0.66 (95% CI: 0.17–1.15), indicating that 66% of ADHD cases in DMP-exposed children with the PON1 CT/TT (rs705381) genotype were due to gene-environment interactions. No significant mediation of HNE-MA was observed between DMP exposure and the risk of ADHD. The estimated proportion mediated was only 7.0% (95% CI: −0.08-0.46). This research suggests the role of OP exposure in the occurrence of ADHD after adjusting for covariates.
AB - This study will help to clarify the relationship between organophosphate pesticides (OPs) and attention deficit/hyperactivity disorder (ADHD) related to oxidative stress and paraoxonases (PON) polymorphisms to further characterize the gene-environment interaction. This case-control study enrolled 85 children with ADHD and 96 control subjects. Urinary OP levels were analyzed by using gas chromatography–mass spectrometry (GC–MS). Oxidative stress biomarkers, such as 8-hydroxy-2-deoxyguanosine (8-OHdG), 8-nitroguanine (8-NO2-Gua), 8-iso-prostaglandin F2α (8-iso-PGF2α), and 4-hydroxy-2-nonenoic acid-mercapturic acid (HNE-MA), were analyzed by using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (S) were calculated to evaluate the additive interactions between OP exposure and PON genetic polymorphism on ADHD. A causal mediation analysis was conducted to clarify the mediation effects of oxidative stress due to OP exposure on ADHD. Children with ADHD had significantly higher DMP (238.95 nmol/g cre. vs. 164.83 nmol/g cre., p value = 0.01) and HNE-MA (30.75 μg/g cre. vs. 18.41 μg/g cre., p value<0.01) concentrations than control children. Children who carried the PON1 GG genotype (rs705379) had low urinary DMP levels, and the level increased with increasing numbers of allele variants. The risk for developing ADHD reached 2.06-fold (OR = 2.06, 95% CI:1.23–3.44) and 1.43-fold (OR = 1.45, 95% CI:1.04–2.03) when the DMP and HNE-MA levels increased by 1 natural log of the concentration, respectively. The estimated AP value was 0.66 (95% CI: 0.17–1.15), indicating that 66% of ADHD cases in DMP-exposed children with the PON1 CT/TT (rs705381) genotype were due to gene-environment interactions. No significant mediation of HNE-MA was observed between DMP exposure and the risk of ADHD. The estimated proportion mediated was only 7.0% (95% CI: −0.08-0.46). This research suggests the role of OP exposure in the occurrence of ADHD after adjusting for covariates.
KW - Additive interaction
KW - Attention deficit/hyperactivity disorder
KW - Organophosphate pesticides
KW - Oxidative stress
KW - Paraoxonases
UR - http://www.scopus.com/inward/record.url?scp=85100627007&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85100627007&partnerID=8YFLogxK
U2 - 10.1016/j.scitotenv.2021.145604
DO - 10.1016/j.scitotenv.2021.145604
M3 - Article
AN - SCOPUS:85100627007
SN - 0048-9697
VL - 773
JO - Science of the Total Environment
JF - Science of the Total Environment
M1 - 145604
ER -