Reevaluation of serum arylesterase activity in neurodevelopmental disorders
Autor: | Catia Rigoletto, Massimo Molteni, Ignazio S. Piras, Laura Altieri, Paolo Curatolo, Stefano Gabriele, Roberto Sacco, Barbara Manzi, Carla Lintas, Federica Lombardi, Maria Nobile, Antonio M. Persico |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
medicine.medical_specialty Physiology Autism Clinical Biochemistry Single-nucleotide polymorphism Specific language impairment behavioral disciplines and activities Biochemistry Arylesterase Attention deficit/hyperactivity disorder (ADHD) Autism spectrum disorder Developmental language disorder Organophosphate Paroxonase Pesticide Article 03 medical and health sciences 0302 clinical medicine Internal medicine mental disorders medicine Allele Molecular Biology biology business.industry lcsh:RM1-950 Paraoxonase Cell Biology medicine.disease PON1 lcsh:Therapeutics. Pharmacology 030104 developmental biology Endocrinology biology.protein business 030217 neurology & neurosurgery |
Zdroj: | Antioxidants Volume 10 Issue 2 Antioxidants, Vol 10, Iss 164, p 164 (2021) |
Popis: | 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. |
Databáze: | OpenAIRE |
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