Decreased serum arylesterase activity in autism spectrum disorders
Open accessAbstract
The PON1 gene, previously found associated with autism spectrum disorders (ASDs), encodes a serum protein responsible for the detoxification of organophosphates (OPs) and able to exert several enzymatic activities. PON1 arylesterase, but not diazoxonase activity, was significantly decreased in 174 ASD patients compared to 175 first-degree relatives and 144 controls (P=2.65×10⁻¹⁶). First degree relatives displayed intermediate activities, closer to patient than to control levels. Differences between patients, first-degree relatives and controls were especially evident among 164 Italians compared to 329 Caucasian-Americans, because arylesterase activity was significantly higher in Italian controls, compared to Caucasian-American controls (P=2.84×10⁻¹⁶). Arylesterase activity and PON protein concentrations were not significantly correlated, supporting a functional inhibition of arylesterase activity in ASD patients over quantitative changes in protein amounts. Serum arylesterase activity, in combination with PON1 genotypes at two single nucleotide polymorphisms (SNPs) known to influence protein amounts (rs705379: C-108T) and substrate specificity (rs662: Q192R), was able to discriminate ASD patients from controls with elevated sensitivity and specificity, depending on genotype and ethnic group. Serum arylesterase activity and genotyping at these two SNPs could thus represent an informative biochemical/genetic test, able to aid clinicians in estimating autism risk in ethnic groups with higher baseline arylesterase activity levels.
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- Authors
- Gaita, L., Manzi, B., Sacco, R., Lintas, C., Altieri, L., Lombardi, F., Pawlowski, T. L., Redman, M., Craig, D. W., Huentelman, M. J., Ober-Reynolds, S., Brautigam, S., Melmed, R., Smith, C. J., Marsillach, J., Camps, J., Curatolo, P., & Persico, A. M.
- Affiliations
- University of Rome Tor Vergata (IT)
- Università Campus Bio-Medico (IT)
- Translational Genomics Research Institute (US)
- Southwest Autism Research & Resource Center (US)
- Hospital Universitari Sant Joan de Reus (ES)
- Corresponding author
- Persico, Antonio M.
- ORCID
- Venue
- Psychiatry Research
- Publisher
- Elsevier BV
- Published
- 2010-12
- Volume
- 180
- Issue
- 2-3
- Pages
- 105-113
- ISSN
- 0165-1781 (ISSN-L)
- OpenAlex
- W2009524935
- Cited by
- 39
- References
- 71
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 4 · 2020: 3 · 2019: 4 · 2018: 1 · 2017: 1 · 2015: 5 · 2014: 4 · 2013: 5 · 2012: 4
- FWCI
- 2.22
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Psychiatry Research (publishedVersion)
- PubMed (publishedVersion)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
- Funders
- Ministero della Salute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Paraoxonase enzyme and polymorphisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
- Keywords
- autism spectrum disorder, paraoxonase 1, arylesterase activity, organophosphate detoxification, single nucleotide polymorphisms, rs662, serum biomarkers, ethnic differences, first-degree relatives
- MeSH terms
- Adolescent, Adult, Carboxylic Ester Hydrolases, Child, Child Development Disorders, Pervasive, Child, Preschool, Enzyme-Linked Immunosorbent Assay, Family, Female, Genetic Testing, Genotype, Humans, Italy, Male, Middle Aged, Gene Expression Regulation, Enzymologic, Statistics, Nonparametric, Polymorphism, Single Nucleotide, Aryldialkylphosphatase, White People, Young Adult
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