Evaluation of pesticide-induced oxidative stress from a gene–environment interaction perspective

Previously we reported that intensive agriculture workers exposed to pesticides had decreased levels of the intraerythrocyte enzymes delta-9-aminolevulinic acid dehydratase (ALA-D) and superoxide dismutase (SOD), very likely as a result of pesticide-induced oxidative stress. We have now examined in this population potential gene–environment interactions by modeling generalized estimating equations (GEE) adjusted for age, sex, body mass index and tobacco and alcohol consumption. Particularly, we assessed the interaction effects between plasma and erythrocyte cholinesterases (BChE and AChE, used as proxies for short- and long-term pesticide exposure, respectively) and a number of genetic polymorphisms of pesticide metabolizing enzymes such as paraoxonase-1 (PON1), glutathione-S-transferases (GST) and plasma cholinesterase variants (BCHE) on levels of erythrocyte antioxidant enzymes (SOD, catalase, glutathione peroxidase, glucose-6-phosphate dehydrogenase and ALA-D). We observed significant interaction effects between BChE activity and PON1192R allele on catalase, glutathione peroxidase and glucose-6-phosphate dehydrogenase activities. BChE also interacted significantly with GSM1 null genotype on ALA-D and SOD. Regarding long-term pesticide exposure, a significant interaction was found between AChE and genotypes PON1192QR and PON1108CC on GR; between AChE and PON1192RR on SOD, and between AChE and GSTM1, GSTT1 and unusual BCHE variants on catalase activity. These findings suggest relevant gene–pesticide interactions and highlight the potential role of genetic risk factors in the pathomechanism of oxidative stress-induced degenerative diseases following pesticide exposure.

► Long-term pesticide exposure decreased CAT activity. ► AChE showed a significant positive association with ALA-D and CAT. ► Only CAT activity was significantly associated with PON1 polymorphisms. ► GSTT1 polymorphism and BCHE variants significantly contributed to ALA-D and SOD. ► Significant gene–environment interactions were observed on antioxidant enzymes.