Biochemical and transcriptomic analysis reveals new metabolites and genes associated with butyrylcholinesterase activity

Background: Butyrylcholinesterase (BChE) is a serine hydrolase enzyme involved in various physiological processes and may act as a biomarker of environmental exposure effects. However, the biochemical and genetic factors influencing its activity remain unclear. Objective: To identify biochemical, hematological, and transcriptomic gene expression factors associated with BChE activity. Methods: Our study analyzed 199 pesticide-exposed agricultural workers in Cajamarca, Peru, assessing biochemical and hematological parameters to predict BChE activity using regression and Random Forest models, complemented by transcriptomic correlation analyses. Results: Data from 199 individuals with occupational pesticide exposure were analyzed. Multiple linear regression models using Box-Cox, logarithmic, and square root transformations, along with a Random Forest algorithm, were evaluated. The logarithmic model showed the best performance. Urea, cholesterol, and triglycerides were identified as the main biochemical predictors of BChE activity. Transcriptomic analysis using data from the Human Protein Atlas revealed that the expression of the genes LIPG and PLTP was positively correlated with BCHE expression, while LIPC, NOS1, and PADI4 showed negative correlations. Conclusion: These findings support the involvement of BChE in lipid and nitrogen metabolism and reinforce its potential use as a biomarker of metabolic disturbances linked to chronic environmental exposure in agricultural populations.