DNA variants and organophosphate neurotoxicity among emerging farmers in the Western Cape of South Africa

BACKGROUND Previous epidemiological studies investigating modification of organophosphate (OP) neurotoxicity by xenobiotic metabolizing enzymes (XMEs) polymorphisms have produced inconsistent results. METHODS A cross-sectional study of 301 emerging farmers was conducted. Neurotoxicity testing included forward and backward recall, digit span, and vibration sensitivity testing. Questionnaire data included demography, potential confounders, and work history of pesticide exposures. Genomic DNA was analyzed from study participants for DNA variants of two glutathione S-transferases (GSTM1 and GSTT1), N-acetyltransferase 2 (NAT2), and Paraoxonase 1 (PON1). RESULTS There was evidence of OP pesticide neurotoxicity modification by rs1799931 (NAT2), rs662 (PON1), and the null allele of GSTM1 in multivariate analysis. The strongest evidence of modification was observed for rs1799931 (NAT2) on the relationship between pesticide poisoning and impaired vibration sense. CONCLUSIONS DNA variants of NAT2, PON1, and GSTM1 may modify OP neurotoxicity, and this requires further exploration.