title: CYP/PON genetic variations as determinant of organophosphate pesticides toxicity.
abstract: In the present scenario of increased accumulation of pesticides in the environment, it is important to understand its impact on human health. The focus is on gene-environment interaction, highlighting the consequences and factors that may halt the biotransformation of some pesticides and change their actual dose response curve due to mixed exposure to pesticides. The paraoxonase and cytochrome P450 gene families are involved in the metabolism of oxon derivate (toxic than its parent compound) of organophosphate pesticides, thus, mutations in these genes may impact the metabolic outcome of pesticides and subsequent health hazards. The complex multi gene-environment interaction and one gene - one risk factor are two different aspects to understand the potential health effect related to environmental exposure studies. The genetic polymorphisms are associated with varying levels of risk within the population, as gene products of varied genotype alter the biotransformation of exogenous/endogenous substrates. This paper is aimed to review the impact of endogenous and exogenous factors on a mechanistic pathway of organophosphate pesticide biotransformation and various risk associated with it among the human population. Understanding the genetic polymorphism of genes involved in pesticide metabolism and highlighting the gene isoform dependent interindividual differences to metabolize particular pesticides may help us to unravel the reasons behind differential toxicity for pesticides exposure than expected.
authors.affiliation: Centre for Environmental Science and Technology,Central University of Punjab, Bathinda 151001, India. sandeep@cup.ac.in.
authors.forename: Gurpreet
authors.initials: G
authors.lastname: Kaur
authors.forename: A K
authors.initials: AK
authors.lastname: Jain
authors.forename: Sandeep
authors.initials: S
authors.lastname: Singh
mesh_terms: D000818:Animals; D043303:Aryldialkylphosphatase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D001711:Biotransformation / Q000187:drug effects / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D004351:Drug Resistance / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D053858:Metabolic Networks and Pathways; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D010575:Pesticides / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D015398:Signal Transduction
chemical_list: D009943:Organophosphorus Compounds; D010575:Pesticides; D003577:Cytochrome P-450 Enzyme System; D043303:Aryldialkylphosphatase