Reevaluation of Serum Arylesterase Activity in Neurodevelopmental Disorders

Organophosphate compounds (OPs) interfere with neurodevelopment and are neurotoxic for humans and animals. They are first biotransformed to the more toxic oxon form, and then hydrolyzed to specific metabolites by the enzyme paraoxonase/arylesterase, encoded by the gene <i>PON1</i> locate...

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Main Authors: Ignazio Stefano Piras, Stefano Gabriele, Laura Altieri, Federica Lombardi, Roberto Sacco, Carla Lintas, Barbara Manzi, Paolo Curatolo, Maria Nobile, Catia Rigoletto, Massimo Molteni, Antonio M. Persico
Format: Article
Language:English
Published: MDPI AG 2021-01-01
Series:Antioxidants
Subjects:
Online Access:https://www.mdpi.com/2076-3921/10/2/164
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author Ignazio Stefano Piras
Stefano Gabriele
Laura Altieri
Federica Lombardi
Roberto Sacco
Carla Lintas
Barbara Manzi
Paolo Curatolo
Maria Nobile
Catia Rigoletto
Massimo Molteni
Antonio M. Persico
author_facet Ignazio Stefano Piras
Stefano Gabriele
Laura Altieri
Federica Lombardi
Roberto Sacco
Carla Lintas
Barbara Manzi
Paolo Curatolo
Maria Nobile
Catia Rigoletto
Massimo Molteni
Antonio M. Persico
author_sort Ignazio Stefano Piras
collection DOAJ
description Organophosphate compounds (OPs) interfere with neurodevelopment and are neurotoxic for humans and animals. They are first biotransformed to the more toxic oxon form, and then hydrolyzed to specific metabolites by the enzyme paraoxonase/arylesterase, encoded by the gene <i>PON1</i> located on human chr. 7q21.3. In autism spectrum disorder (ASD) and in attention-deficit/hyperactivity disorder (ADHD), a correlation between OP exposure and disease onset has been reported. In this case-control study, we aimed to replicate our previous work showing reduced levels of serum PON1 arylesterase activity in Italian and Caucasian-American ASD samples, and to extend our analysis to other neurodevelopmental disorders, namely ADHD and developmental language disorder (DLD), also known as specific language impairment (SLI). The arylesterase activity, measured using standard spectrophotometric methods, is significantly reduced in the ADHD, and not in the ASD sample compared with the controls. Our previous results seemingly stem from spuriously high arylesterase levels in the former control sample. Finally, genotyping SNPs rs705379 and rs662 using TDI-FP, a significant effect of rs705379 alleles on the serum arylesterase activity is observed in all of the subgroups tested, regardless of diagnosis, as well as a lack of association between <i>PON1</i> gene polymorphisms and ASD/ADHD susceptibility in the Italian population. In summary, the serum arylesterase activity is reduced in children and adolescents with ADHD, and this reduction is not due to the functional <i>PON1</i> gene variants assessed in this study. Based on previous literature, it may more likely reflect enhanced oxidative stress than specific genetic underpinnings.
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spelling doaj.art-a89c555d26e948cda00d25cc88e6a03b2023-12-03T14:20:06ZengMDPI AGAntioxidants2076-39212021-01-0110216410.3390/antiox10020164Reevaluation of Serum Arylesterase Activity in Neurodevelopmental DisordersIgnazio Stefano Piras0Stefano Gabriele1Laura Altieri2Federica Lombardi3Roberto Sacco4Carla Lintas5Barbara Manzi6Paolo Curatolo7Maria Nobile8Catia Rigoletto9Massimo Molteni10Antonio M. Persico11Unit of Child & Adolescent Neuropsychiatry, University Campus Bio-Medico, I-00128 Rome, ItalyUnit of Child & Adolescent Neuropsychiatry, University Campus Bio-Medico, I-00128 Rome, ItalyUnit of Child & Adolescent Neuropsychiatry, University Campus Bio-Medico, I-00128 Rome, ItalyUnit of Child & Adolescent Neuropsychiatry, University Campus Bio-Medico, I-00128 Rome, ItalyUnit of Child & Adolescent Neuropsychiatry, University Campus Bio-Medico, I-00128 Rome, ItalyUnit of Child & Adolescent Neuropsychiatry, University Campus Bio-Medico, I-00128 Rome, ItalyUnit of Child and Adolescent Neuropsychiatry, University of Rome “Tor Vergata”, I-00133 Rome, ItalyUnit of Child and Adolescent Neuropsychiatry, University of Rome “Tor Vergata”, I-00133 Rome, ItalyChild Psychopathology Unit, Scientific Institute, IRCCS ‘E. Medea’, I-23842 Bosisio Parini (LC), ItalyChild Psychopathology Unit, Scientific Institute, IRCCS ‘E. Medea’, I-23842 Bosisio Parini (LC), ItalyChild Psychopathology Unit, Scientific Institute, IRCCS ‘E. Medea’, I-23842 Bosisio Parini (LC), ItalyInterdepartmental Program “Autism 0–90”, “G. Martino” University Hospital, University of Messina, I-98122 Messina, ItalyOrganophosphate compounds (OPs) interfere with neurodevelopment and are neurotoxic for humans and animals. They are first biotransformed to the more toxic oxon form, and then hydrolyzed to specific metabolites by the enzyme paraoxonase/arylesterase, encoded by the gene <i>PON1</i> located on human chr. 7q21.3. In autism spectrum disorder (ASD) and in attention-deficit/hyperactivity disorder (ADHD), a correlation between OP exposure and disease onset has been reported. In this case-control study, we aimed to replicate our previous work showing reduced levels of serum PON1 arylesterase activity in Italian and Caucasian-American ASD samples, and to extend our analysis to other neurodevelopmental disorders, namely ADHD and developmental language disorder (DLD), also known as specific language impairment (SLI). The arylesterase activity, measured using standard spectrophotometric methods, is significantly reduced in the ADHD, and not in the ASD sample compared with the controls. Our previous results seemingly stem from spuriously high arylesterase levels in the former control sample. Finally, genotyping SNPs rs705379 and rs662 using TDI-FP, a significant effect of rs705379 alleles on the serum arylesterase activity is observed in all of the subgroups tested, regardless of diagnosis, as well as a lack of association between <i>PON1</i> gene polymorphisms and ASD/ADHD susceptibility in the Italian population. In summary, the serum arylesterase activity is reduced in children and adolescents with ADHD, and this reduction is not due to the functional <i>PON1</i> gene variants assessed in this study. Based on previous literature, it may more likely reflect enhanced oxidative stress than specific genetic underpinnings.https://www.mdpi.com/2076-3921/10/2/164arylesteraseattention deficit/hyperactivity disorder (ADHD)autismautism spectrum disorderdevelopmental language disorderorganophosphate
spellingShingle Ignazio Stefano Piras
Stefano Gabriele
Laura Altieri
Federica Lombardi
Roberto Sacco
Carla Lintas
Barbara Manzi
Paolo Curatolo
Maria Nobile
Catia Rigoletto
Massimo Molteni
Antonio M. Persico
Reevaluation of Serum Arylesterase Activity in Neurodevelopmental Disorders
Antioxidants
arylesterase
attention deficit/hyperactivity disorder (ADHD)
autism
autism spectrum disorder
developmental language disorder
organophosphate
title Reevaluation of Serum Arylesterase Activity in Neurodevelopmental Disorders
title_full Reevaluation of Serum Arylesterase Activity in Neurodevelopmental Disorders
title_fullStr Reevaluation of Serum Arylesterase Activity in Neurodevelopmental Disorders
title_full_unstemmed Reevaluation of Serum Arylesterase Activity in Neurodevelopmental Disorders
title_short Reevaluation of Serum Arylesterase Activity in Neurodevelopmental Disorders
title_sort reevaluation of serum arylesterase activity in neurodevelopmental disorders
topic arylesterase
attention deficit/hyperactivity disorder (ADHD)
autism
autism spectrum disorder
developmental language disorder
organophosphate
url https://www.mdpi.com/2076-3921/10/2/164
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