Association Between Human Paraoxonase Gene Polymorphism and Chronic Symptoms in Pesticide-Exposed Workers

Abstract

Pesticides, such as parathion, are metabolized by cytochrome p-450 system to paraoxon, which is a potent cholinesterase inhibitor. Paraoxonase (PON) catalyzes the hydrolysis of these toxic metabolites and protects against pesticide toxicity. A glutamine/arginine (Gln/Arg) polymorphism at amino acid position 192 of PON has been described. The Arg/Arg genotype is associated with higher serum paraoxonase activity compared to Gln/Gln. The Arg/Gln genotype is associated with intermediate serum PON activity. The potential association between PON genotype and symptoms of chronic pesticide toxicity was examined among 100 farm workers. As part of a cross-sectional study of pesticide toxicity among mixed-race farm workers in the Western Cape. South Africa, 100 farm workers were genotyped for polymorphism of the paraoxonase gene at amino acid position 192. Subjects with two or more of the following symptoms were considered to have evidence of chronic toxicity: abdominal pain, nausea, rhinorrhea, dizziness, headache, somnolence, fatigue, gait disturbance, limb numbness, paresthesias, limb pain, or limb weakness. In multivariable logistic regression analysis, the independent predictors of chronic toxicity were previous history of head trauma resulting in loss of consciousness (OR 2.8, 95% CI = 1.7-6.7), having worked as a pesticide applicator (OR 5.4, 95% CI = 3.2-8.9), and having one of the two "slow metabolism" (Gln/Gln or Gln/Arg) genotypes (OR 2.9, 95% CI = 1.7-6.9). Furthermore, the prevalence of chronic toxicity increased in a stepwise fashion from 15% among pesticide nonapplicators with a "fast metabolism" (Arg/Arg) genotype, to 42.9% among pesticide nonapplicators with "slow metabolism" (Gln/Gln or Gln/Arg) genotypes, to 58.8% among pesticide applicators with "fast metabolism" genotype, and 75.0% among pesticide applicators with "slow metabolism" genotypes (P = 0.001). Age, number of years on the job, smoking history, alcohol history, education level, plasma or red blood cell cholinesterase level, or previous history of acute organophosphate poisoning were not statistically significant predictors of chronic toxicity. The PON genotype is an important determinant of a farmworker's susceptibility to chronic pesticide poisoning.

Occupational Safety of Farmers in the Vegetable Industry

“…In a study of Japanese farmers, exposure also occurred during spraying and pesticide poisoning led to acute dermatitis (5%) and chemical burns (3%) [25]. Lee, London, Paulauskis et al's study showed that working as a pesticide applicator was a predictor of chronic toxicity that included abdominal pain, nausea, rhinorrhea, dizziness, headache, somnolence, fatigue, gait isturbance, limb numbness, paresthesias, limb pain and limb weakness [22].…”

“…Other research showed a link between pesticide exposure and adverse effects on children and fetuses such as low birth weight [17,18], preterm birth or toxemia [19], stillborn infants [20] and miscarriages [21]. In China's Anhui province, DDT was associated with miscarriages in the first few weeks of pregnancy [22]. In Ecuador, women exposed to pesticides in the cut-flower industry were at risk of spontaneous abortion [23].…”

Paraoxonase status and plasma butyrylcholinesterase activity in chlorpyrifos manufacturing workers

“…For example, the PON1 192R alloform hydrolyzes paraoxon in vitro with greater catalytic efficiency than does the PON1 192Q alloform, whereas the PON1 192 alloforms hydrolyze diazinon oxon (diazoxon) with nearly equivalent catalytic efficiencies (Haley et al, 1999;Furlong et al, 2000b;Lee et al, 2003). In each example, the PON1 192QR genotype shows an intermediate activity relative to the PON1 192RR and PON1 192QQ alloforms.…”

Serum Paraoxonase-1 (PON-1) Genotype and Exposure to Organophosphorous Insectides—Is There a High-Risk Population?

“…This finding was likely because non-applicators are still exposed to OP pesticides through other indirect means. Interestingly, in this study, neither RBC nor plasma cholinesterase levels were statistically significant predictors of chronic cholinergic toxicity [13].…”