Background Modulation of organophosphate (OP) neurotoxicity by genetic polymorphisms of xenobiotic metabolising enzymes (XMEs) has not previously been investigated

Objectives To investigate whether XMEs polymorphisms modify OP neurotoxicity among emerging farmers.

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 analysed from study participants for DNA variants of two glutathione S-transferases (GST), N-acetyltransferase 2 (NAT2) and Paraoxonase 1 (PON1).

Results The median age of workers was 39 years (range: 30–48 years) of whom 54% were OP pesticide applicators. There was a low prevalence of the null genotype for GSTT1 (1%) and for GSTM1 (16%), while the genotypic frequency for the GA and AA grouping of rs1799931 (NAT2) was 10%. 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. The increased prevalence of impaired vibration sense in OP poisoned compared to non-poisoned workers (Odds ratio=5.7, 95% confidence interval (CI): 1.4–22.7) was higher among those with the GG genotype than those with the GA and AA genotypes (Odds ratio=1.5, CI: 0.1–43.2).

Conclusion DNA variants of NAT2, PON1 and GSTM1 may modify OP neurotoxicity and this requires further exploration