Association between urinary organophosphate pesticide metabolites and blood lipid levels in US children.

BACKGROUND

While previous studies showed associations between greater organophosphate pesticide (OPP) exposure and higher blood cholesterol levels in adults, the association in children and its underlying mechanism remain unclear. We investigated the association between urinary dialkylphosphate concentrations (DAP), which reflect recent OPP exposure, and blood lipid levels in preadolescent children. We examined the effect of OPP exposure on mouse hepatic transcription factors to explore underlying mechanisms.

METHODS

Using data from the National Health and Nutrition Examination Survey 1999-2002, we examined the association between DAP and blood lipid levels in 385 children aged 6-11 years, using Bayesian linear regression adjusted for potential confounders. The association between DAP and the presence of dyslipidemia was examined by Bayesian logistic regression. Using published RNA-seq data of mouse liver, we evaluated the relative abundances of target gene expressions of transcription factors relevant to hepatic lipid metabolism in mice on a fenthion-containing diet and a control diet.

RESULTS

Over 50 % of children had detectable levels of dimethylphosphate, diethylphosphate, dimethylthiophosphate, and diethylthiophosphate. Higher diethylthiophosphate was associated with high total cholesterol level (highest vs lowest quartile group: odds ratio = 4.35, 95 % credible interval = 1.63-11.70). Target gene-set analyses revealed higher expression of PPARα and PPARγ target genes upon fenthion exposure, suggesting upregulated fatty acid oxidation and triglyceride synthesis, resembling transcriptomic changes observed in non-alcoholic fatty liver disease.

CONCLUSION

Higher diethylthiophosphate was associated with high blood cholesterol levels. Upregulated PPARα and PPARγ target genes may partly explain the association between OPP exposure and dyslipidemia.