Reevaluation of serum arylesterase activity in neurodevelopmental disorders

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

Research output: Contribution to journalArticlepeer-review

Abstract

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 PON1 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 PON1 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 PON1 gene variants assessed in this study. Based on previous literature, it may more likely reflect enhanced oxidative stress than specific genetic underpinnings.

Original languageEnglish
Article number164
Pages (from-to)1-14
Number of pages14
JournalAntioxidants
Volume10
Issue number2
DOIs
Publication statusPublished - Feb 2021

Keywords

  • Arylesterase
  • Attention deficit/hyperactivity disorder (ADHD)
  • Autism
  • Autism spectrum disorder
  • Developmental language disorder
  • Organophosphate
  • Paroxonase
  • Pesticide
  • Specific language impairment

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Fingerprint Dive into the research topics of 'Reevaluation of serum arylesterase activity in neurodevelopmental disorders'. Together they form a unique fingerprint.

Cite this