Tipping the Balance of Autism Risk

Potential Mechanisms Linking Pesticides and Autism

Janie F. Shelton; Irva Hertz-Picciotto; Isaac N. Pessah

Disclosures

Environ Health Perspect. 2012;120(7):944-951. 

In This Article

Vulnerable Genetic Subpopulations

The primary neurological targets of commonly used insecticides (Scharf 2003) can be paired with vulnerable genetic subpopulations that may be at increased risk for autism (Table 1). Because of both the large number of genetic alterations and gene × gene interactions that have been implicated in autism, and the phenotypic heterogeneity in cases, the notion that a single environmental exposure can be to blame for the majority of cases is unrealistic. Also, because the dosage of pesticides to nonoccupationally exposed women is likely to be lower than that required to induce the mechanisms of injury observed in many animal models, genetic susceptibility becomes a critical factor in this discussion.

In 2001, the reelin gene was implicated in autism risk when repeats (11+) in the 5' untranslated region were associated with 72% transmission to affected siblings and only 32% transmission to unaffected siblings (Persico et al. 2001). The proteolytic activity of reelin on extracellular matrix proteins that control neuronal migration is significantly inhibited by OP pesticides (Sinagra et al. 2008), and OP metabolism efficiency is regulated by the gene for paraoxonase 1 (PON1) (Mackness et al. 1997). Interestingly, an association between less active forms of the PON1 gene and autism was observed in Caucasian families in North America, but not in Italian families, leading authors to hypothesize that the slow metabolizing polymorphism confers risk in areas with high levels of OPs but may not affect autism risk otherwise (D'Amelio et al. 2005).

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