The Impact of Pesticides - Academy Publish

and parathion) showed that carriers of the variant PON1 55MM genotype exposedto diazinon or chlorpyrifos exhibited a two- and three-fold increase, respectively inthe risk of having Parkinson's disease compared to unexposed wild-type orheterozygous individuals; no increase in risk was noted for parathion. Authorsconclude the importance of considering susceptibility factors when studyingenvironmental exposures in Parkinson's disease (Manthripragada et al., 2010).Similar results reporting that the 55M allele was associated with Parkinson's diseasehave been reported by others (Carmine et al., 2002; Fong et al., 2005). By thecontrary, there are some studies that were not able to show significant associationsbetween PON1 Q192R polymorphism and Parkinson's disease (Benmoyal-Segal etal., 2005; Dick et al., 2007; Taylor et al., 2002).Another neurodegenerative disease that has been related to OP exposure isAlzheimer’s disease, the most common cause of dementia in old-aged individuals,which is a complex disorder with a multi-factorial etiology (Cellini et al., 2006). It ischaracterized by: 1) deposition of oxidized low-density lipoproteins (LDL) formingthe senile plaques, 2) structural changes in neurons, and 3) cell death inacetylcholine-producing neurons (Pola et al., 2003). Also, the implication ofvascular factors in Alzheimer-type dementia is strongly suspected (Dantoine et al.,2002a). Studies in last decades have observed a significant association betweenAlzheimer's disease and pesticides exposure. Baldi et al. (2001) showed in aprospective cohort study of 1,507 French elderly a relative risk of Alzheimer'sdisease of 2.39 (95%CI 1.02 -5.63) for occupational exposure to pesticides(dithiocarbamates, carbamates and OP, among others) and 5.63 (95%CI 1.47 -21.58) for Parkinson's disease after confounding factors were controled. It was notpossible to identify the specific pesticides responsible for these observed effects.Similarly, Hayley et al. (2010) reported an association of Alzheimer's disease withOP pesticide exposure (hazard ratio (HR) of 1.53, 95%CI 1.05-2.23) in residents ofan agricultural community, concluding that pesticide exposure may increase the riskof dementia and Alzheimer's disease later in life.Serum PON1 activity decreases with aging and in disorders associated with a highrisk of adverse cardiovascular events; therefore epidemiological studies have shownthat PON1 activity is negatively correlated with vascular dementia. Additionally,there are studies showing the association between PON1 polymorphisms and thepresence of Alzheimer's disease. In this regard, polymorphism PON1 Q192R wasreported as a reliable marker to distinguish patients with Alzheimer's disease frompatients with vascular dementia or healthy subjects (Dantoine et al., 2002b; He etal., 2006; Scacchi et al., 2003). However, other studies have failed to found thisassociation (Pola et al., 2003; Wingo et al., 2012) There have also been reported thatthe frequency of PON1 55MM genotype was significantly increased in Alzheimer'sdisease in patients from Canada (Leduc and Poirier, 2008). The role of PON1polymorphisms in the promoter region is also controversial. Some results indicatedthat PON1 C-161T polymorphism does not play a role in Alzheimer's disease(Cellini et al., 2006), while there is evidence of the association between PON1 C-161T polymorphic site and Alzheimer's disease in Caucasians and AfricanAmericans (Erlich et al., 2006). A recent mini review concluded that theinvolvement of PON1 genotypes in the occurrence of neurodegenerative diseasesremains unclear (Androustsopoulos et al., 2011).Due to the complexity of the neurodegenerative diseases, and the inconsistency ofpublished results, more studies are necessary to further clarify the effect of geneenvironmentinteractions of PON1 in the development of diseases.AcademyPublish.org - The Impact of Pesticides67