Paraoxonase and susceptibility to organophosphorus poisoning in farmers dipping sheep

Abstract

The farmers reporting chronic ill health due to organophosphate exposure have a higher proportion of the PON1-192R polymorphism associated with lower rates of diazoxon hydrolysis and lower rates of diazoxon hydrolysis than the controls and that their ill health may be explained by a lower ability to detoxify diazoxon.

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

“…Although the prevalence of these OP genotypes varies in different setting, those of the minor alleles were low when compared to previous studies. 2,18,19 The combination of genotypic groups might also have resulted in the combination of risk and non-risk alleles, which would dilute the exposure/outcome association and shift it to the null.…”

“…22 Although very few epidemiological studies have been conducted to determine the effects of the polymorphism on OP toxicity, all the published studies have reported the importance of PON1 and its allelic variants on OP susceptibility. 2,3,23,24 Furthermore, these studies were conducted in various settings, used different study designs, and investigated diverse health outcomes. These investigations focused on individuals exposed to OPs through sheep dipping in the UK, 2 poisoning of persons through suicide attempts (either orally or through an injection) in Turkey, 25 OP sprayers from public health programmes in India and South African farm workers.…”

“…2,3,23,24 Furthermore, these studies were conducted in various settings, used different study designs, and investigated diverse health outcomes. These investigations focused on individuals exposed to OPs through sheep dipping in the UK, 2 poisoning of persons through suicide attempts (either orally or through an injection) in Turkey, 25 OP sprayers from public health programmes in India and South African farm workers. 3,23 However, none of these studies investigated neurobehavioral performance as an outcome of interest.…”

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

“…They found that individuals with the PON-1 RR192 and PON-1 LL55 allele were more likely to report symptoms of chronic OP exposure and feel ill, as compared to similarly employed controls who believed themselves to be healthy. This finding is likely due to the fact that individuals expressing the PON-1 RR192 and PON-1 LL55 alloforms are less efficient at hydrolyzing diazoxon, the major metabolite of diazinon, an OP found in the sheep dip [12].…”

“…In addition, slow metabolizers who also expressed PON-1 LL55 , which is associated with decreased PON-1 activity, were found to be the most likely persons to report symptoms of OP toxicity. [12] In addition, PON-1 fast metabolizers have been shown to have higher plasma and RBC cholinesterase levels than their counterparts who are slow metabolizers. [14] Together, these studies suggest a protective effect against OP toxicity in individuals who are PON-1 rapid metabolizers and have higher PON-1 activity.…”