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

Abstract

The Health Studies Branch (HSB) is responsible for responding to domestic and international requests for assistance with suspected and known environmental-associated public health threats as well as pursuing original environmental research. The HSB employs personnel with a wide variety of educational backgrounds and professional training including epidemiology, medicine, toxicology, statistics, and other environmental public health-related disciplines. This wide range of expertise is necessary to address the broad scope of potential environmental health threats. HSB scientists conduct studies on environmental exposures. Recent examples include the following: mercury exposure in children living in large urban areas, exposure to brevetoxins and microcystins arising from harmful algal blooms, and occupational exposures to pesticides. This article will present a brief description of an ongoing study of insecticide exposure and paraoxonase-1 (PON-1) genotype in banana plantation workers in Chinandega, Nicaragua. We will then discuss the enzyme PON-1 and its potential role in organophosphate insecticide metabolism and toxicity.Keywords PON-1 . OrganophosphateInvestigators: Health Studies branch, division of Environmental Health/Health Effects, in the National Center for Environmental HealthThe Health Studies Branch (HSB) is responsible for responding to domestic and international requests for assistance with suspected and known environmental-associated public health threats as well as pursuing original environmental research. The HSB employs personnel with a wide variety of educational backgrounds and professional training including epidemiology, medicine, toxicology, statistics, and other environmental public health-related disciplines. This wide range of expertise is necessary to address the broad scope of potential environmental health threats. HSB scientists conduct studies on environmental exposures. Recent examples include the following: mercury exposure in children living in large urban areas [1,2], exposure to brevetoxins and microcystins arising from harmful algal blooms [3], and occupational exposures to pesticides. This article will present a brief description of an ongoing study of insecticide exposure and paraoxonase-1 (PON-1) genotype in banana plantation workers in Chinandega, Nicaragua. We will then discuss the enzyme PON-1 and its potential role in organophosphate (OP) insecticide metabolism and toxicity.Current CDC Activity: PON-1 and Chlorpyrifos Exposure Among Agricultural Workers Paraoxonase-1, a serum enzyme closely associated with high-density lipoprotein (HDL), plays a role in lipid and OP metabolism. Various mutations in the PON-1 gene are known to determine the efficacy of OP metabolism by PON-1. Animal studies show that PON-1 genotype and the rate of OP metabolism play a major role in determining resistance to the acute toxicity of OPs [4]. However, the

Acute Changes in Thyroid Hormone Levels among Thai Pesticide Sprayers

“…The simple before and after comparisons do not account for these differences or any individual differences in the ability to metabolize and excrete these pesticides. For example, polymorphisms in the genotype of PON-1, an enzyme that metabolizes OP pesticides, have been shown to directly impact susceptibility to OP toxicity [ 71 ]. In addition, unlike the simple paired comparison, the models adjusted for the impact of other potential confounders and covariates such as age, gender, smoking, stress etc.…”

Evaluating the link between Paraoxonase-1 levels and Alzheimer's disease development

“…The PON1 gene has two common single nucleotide polymorphisms (SNPs) in the coding region that have been extensively studied: Gln (Q)/Arg (R) substitution at position 192 and Leu(L)/Met(M) substitution at position 55. 22,23,29 While L55M SNP affects the concentration of enzyme, Q192R markedly and selectively affects the catalytic efficiency of PON1 in hydrolyzing paraoxon, chlorpyrifos oxon, and the nerve agents sarin and soman. 29 At present, the most convincing proofs for the role of PON1 in driving OP sensitivity come from animal experiments.…”

“…22,23,29 While L55M SNP affects the concentration of enzyme, Q192R markedly and selectively affects the catalytic efficiency of PON1 in hydrolyzing paraoxon, chlorpyrifos oxon, and the nerve agents sarin and soman. 29 At present, the most convincing proofs for the role of PON1 in driving OP sensitivity come from animal experiments. 23,30 Animal species with lower PON1 serum activity are more susceptible to OP exposures (e.g.…”

Occupational exposure to pesticides as a possible risk factor for the development of chronic diseases in humans

“…The administration of methoxyclor, an organochlorine used as an insecticide, disrupts the female offspring reproductive capacity by remodelling the expression of sex hormones (56). As regards the regulatory role of epigenetics in pesticide toxicology, Holland et al (57) investigated the role of paraoxonase 1 (PON1), a multifunctional enzyme particularly implicated in the metabolism of organophosphates (58,59). PON1 activity varies significantly among individuals, and several molecular variants of this enzyme are recognised.…”