Paraoxonase gene variants are associated with autism in North America, but not in Italy: Possible regional specificity in gene-environment interactions

M. D'Amelio, I. Ricci, R. Sacco, X. Liu, L. D'Agruma, L. A. Muscarella, V. Guarnieri, R. Militerni, C. Bravaccio, M. Elia, C. Schneider, R. Melmed, S. Trillo, T. Pascucci, S. Puglisi-Allegra, K. L. Reichelt, F. Macciardi, J. J A Holden, A. M. Persico

Research output: Contribution to journalArticlepeer-review

Abstract

Organophosphates (OPs) are routinely used as pesticides in agriculture and as insecticides within the household. Our prior work on Reelin and APOE delineated a gene-environment interactive model of autism pathogenesis, whereby genetically vulnerable individuals prenatally exposed to OPs during critical periods in neurodevelopment could undergo altered neuronal migration, resulting in an autistic syndrome. Since household use of OPs is far greater in the USA than in Italy, this model was predicted to hold validity in North America, but not in Europe. Here, we indirectly test this hypothesis by assessing linkage/association between autism and variants of the paraoxonase gene (PON1) encoding paraoxonase, the enzyme responsible for OP detoxification. Three functional single nucleotide polymorphisms, PON1 C-108T, L55M, and Q192R, were assessed in 177 Italian and 107 Caucasian-American complete trios with primary autistic probands. As predicted, Caucasian-American and not Italian families display a significant association between autism and PON1 variants less active in vitro on the OP diazinon (R192), according to case-control contrasts (Q192R: χ2=6.33, 1 df, P2=5.26, 1 df, P

Original languageEnglish
Pages (from-to)1006-1016
Number of pages11
JournalMolecular Psychiatry
Volume10
Issue number11
DOIs
Publication statusPublished - Nov 2005

Keywords

  • APOE
  • Autistic disorder
  • Chlorpyrifos
  • Diazinon
  • Organophosphates
  • Reelin

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health

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