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.

中文翻译：

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在神经发育障碍中重新评估血清芳基酯酶活性

有机磷酸酯化合物（OPs）会干扰神经发育，并对人类和动物具有神经毒性。它们首先被生物转化为毒性更高的oxon形式，然后通过由PON1基因编码的对氧磷酶/芳基酯酶水解为特定的代谢物。位于人类的hr。7q21.3。在自闭症谱系障碍（ASD）和注意力不足/多动障碍（ADHD）中，已经报道了OP暴露与疾病发作之间的相关性。在本病例对照研究中，我们旨在复制我们先前的工作，这些工作显示意大利和白种人ASD样品中血清PON1芳基酯酶活性降低，并将我们的分析扩展到其他神经发育障碍，即ADHD和发育语言障碍（DLD） ，也称为特定语言障碍（SLI）。与对照组相比，使用标准分光光度法测量的芳基酯酶活性在ADHD中显着降低，而在ASD样品中则没有。我们以前的结果似乎源于前一个对照样品中假性很高的芳基酯酶水平。最后，PON1基因多态性和ASD / ADHD在意大利人群中的易感性。总之，患有ADHD的儿童和青少年的血清芳基酯酶活性降低，并且这种降低不是由于本研究中评估的功能性PON1基因变体。根据以前的文献，与特定的遗传基础相比，它更可能反映出增强的氧化应激。