Genes May Enhance Ill Health From Organophosphate Exposure
By Harvey McConnell
Some farmers appear to have a genetic predisposition to the adverse health effects associated with exposure to organophosphate in sheep dip.
Results of a study by Dr Nicola Cherry and colleagues from the University of Manchester "provide support for those who believe that repeated exposure to organophosphates may cause chronic ill health."
Exposure to organophosphates has acute effects on health, but evidence of chronic effects is unclear. Many people who have been occupationally exposed to these chemicals, especially in sheep farming, think them to be a cause of poor health.
Clinicians explain that human serum paraoxonase (PON1) hydrolyses organophosphates. Isoforms of the enzyme, which differ in their PON1 activity, result from aminoacid substitutions at positions 192 (glutamine to arginine) and 55 (leucine to methionine). The effect of the 192 polymorphism depends upon the substrate; diazinonoxon, the active metabolite of diazinon, an organophosphate often used in sheep dip chemicals in the UK, is hydrolysed more slowly by the R than the Q alloenzyme.
Dr Cherry investigated the relation between genetic variations in the gene regulating paraoxonase and health outcomes in farmers. The researchers recruited 175 farmers who reported ill health attributed to exposure to sheep dip. In turn, the farmers nominated 234 other farmers who also dipped sheep and whom they believed to be in good health.
Researchers calculated the odds ratios for polymorphisms in the gene regulating paraoxonase, and therefore the ability to break down toxic organophosphates. Farmers who reported poor health were nearly twice as likely than the healthy farmers to have specific alterations in the gene regulating paraoxonase.
These farmers were more likely to have at least one R allele at position 192 (glutamine to arginine aminoacid substitution; odds ratio 1.93, 95 percent CI 1.24-3.01), both alleles of type LL (1.70, 1.07-2.68) at position 55, and to have diazoxonase activity below normal median (1.77, 1.18"2.67).
"Our results support the hypothesis that organophosphates contribute to the reported ill health of people who dip sheep, " the researchers said.
Dr Cherry in comments, said: "The study was set up to test a clear hypothesis, that those whose genes produced a less efficient enzyme would, if exposed to organophosphates, be more likely to become ill.
"The results provide support for those who believe that repeated exposure to organophosphates may cause chronic ill health. Sheep dippers in the UK are one important group, but there are many others world-wide who are exposed to these chemicals and whose health may be affected as a result."
Lancet 2002; 359: 763-64.
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