Pesticide exposure on southwestern Taiwanese with MnSOD and NQO1 polymorphisms is associated with increased risk of Parkinson's disease

ArticleinClinica Chimica Acta 378(1-2):136-41 · March 2007with10 Reads
DOI: 10.1016/j.cca.2006.11.006 · Source: PubMed
Hypothetic mechanism of the individual vulnerability to oxidative stress through metabolism of environmental xenobiotics and genotypic polymorphisms has been considered to promote the development of Parkinson's disease (PD). In this case-control study, we determined the role of manganese-containing superoxide dismutase (MnSOD) and NAD(P)H: quinone oxidoreductase 1 (NQO1) genes in PD risk in a population with high prevalence of pesticide exposure. From southwestern region of Taiwan, we enrolled 153 patients with idiopathic PD and 155 healthy control subjects matched for age, sex and origin. Detailed questionnaires of face-to-face interviews among these subjects were collected. PCR-based restriction fragment length polymorphism (RFLP) assays were used to determine the genotypes of MnSOD (-9 T>C) and NQO1 (609 C>T) genes. Exposure to pesticides associated with PD was significant among patients with an increased odds ratio (OR) of 1.69 (95%CI, 1.07-2.65), and this association remained significant after adjustment for age, sex, and cigarette smoking (aOR=1.68, 95%CI, 1.03-2.76, P=0.023). Considering genetic factors, there were no significant differences in frequencies of both genotypes of MnSOD and NQO1 polymorphisms between PD patients and the control subjects (P>0.05). However, this difference in genotype distribution was significant among subjects who had been exposed to pesticide, with aOR of 2.49 (95%CI, 1.18-5.26, P=0.0072) for MnSOD C allele and aOR of 2.42 (95%CI, 1.16-4.76, P=0.0089) for NQO1 T allele, respectively. Moreover, among subjects exposed to pesticide, the combined MnSOD/NQO1 variant genotype was significantly associated with a 4.09-fold increased risk of PD (95%CI, 1.34-10.64, P=0.0052). Susceptible variants of MnSOD and NQO1 genes may interact with occupational pesticide exposure to increase PD risk in southwestern Taiwanese.
    • "However, studies performed by Singh et al. [133] and Grasbon-Frodl et al. [134] were contradictory, suggesting gene–environment or gene–gene interactions between PD and MnSOD. This hypothesis is corroborated by a study by Fong et al. [135], which found an association between the Ala allele and PD in subjects exposed to pesticide. Similar to AD, increased MnSOD enzyme efficiency could increase vulnerability to development of PD. "
    [Show abstract] [Hide abstract] ABSTRACT: Oxidative stress is characterized by imbalanced reactive oxygen species (ROS) production and antioxidant defenses. Two main antioxidant systems exist. The nonenzymatic system relies on molecules to directly quench ROS and the enzymatic system is composed of specific enzymes that detoxify ROS. Among the latter, the superoxide dismutase (SOD) family is important in oxidative stress modulation. Of these, manganese-dependent SOD (MnSOD) plays a major role due to its mitochondrial location, i.e., the main site of superoxide ( [Formula: see text] ) production. As such, extensive research has focused on its capacity to modulate oxidative stress. Early data demonstrated the relevance of MnSOD as an [Formula: see text] scavenger. More recent research has, however, identified a prominent role for MnSOD in carcinogenesis. In addition, SOD downregulation appears associated with health risk in heart and brain. A single nucleotide polymorphism which alters the mitochondria signaling sequence for the cytosolic MnSOD form has been identified. Transport into the mitochondria was differentially affected by allelic presence and a new chapter in MnSOD research thus begun. As a result, an ever-increasing number of diseases appear associated with this allelic variation including metabolic and cardiovascular disease. Although diet and exercise upregulate MnSOD, the relationship between environmental and genetic factors remains unclear. © 2015 Elsevier Inc. All rights reserved.
    Full-text · Article · Apr 2015
    • "Inadequate sample sizes. The sample size was inadequate (i.e. 150 cases) in many studies (Dhillon et al., 2008; Fong et al., 2007; Frigerio et al., 2006; Godeiro et al., 2010; Pereira and Garrett, 2010; Richardson et al., 2011; Wright and Keller-Byrne, 2005). When exposure strata contain few subjects, even slight misclassifications of diagnosis or exposure can substantially alter the associations observed. "
    [Show abstract] [Hide abstract] ABSTRACT: It has been suggested that exposure to pesticides might be involved in the etiology of Parkinson's disease (PD). We conducted an updated systematic review of the epidemiologic literature over the past decade on the relationship between pesticide exposure and PD, using the MEDLINE database. Despite methodological differences, a significantly increased PD risk was observed in 13 out of 23 case-control studies that considered overall exposure to pesticides (risk estimates of 1.1-2.4) and in 10 out of 12 studies using other research designs (risk estimates of 2 or higher). Various studies found stronger associations in genetically susceptible individuals. Among a growing number of studies on the effects of exposure to specific pesticides (n=20), an increased PD risk has been associated with insecticides, especially chlorpyrifos and organochlorines, in six studies (odds ratios of 1.8-4.4), and with the herbicide paraquat, the fungicide maneb or the combination of both. Findings considerably strengthen the evidence that exposure to pesticides in well water may contribute to PD, whereas studies of farming and rural residence found inconsistent or little association with the disease. Taken together, this comprehensive set of results suggests that the hypothesis of an association between pesticide exposure and PD cannot be ruled out. However, inadequate data on consistent responses to exposure hinder the establishment of a causal relationship with PD. Given the extensive worldwide use of many pesticides, further studies are warranted in larger populations that include detailed quantitative data on exposure and determination of genetic polymorphisms.
    Full-text · Article · May 2012
    • "Mitochondrial ROS are a key component to PD development [397], with complex I of the electron transport chain acting as both a victim, and source, of ROS [122,125,397]. Several studies demonstrate that while polymorphisms of the MnSOD gene associated with other diseases, namely the Val16Ala and Ile58Thr polymorphisms, are not associated with PD risk398399400, the Val16Ala polymorphism is linked to PD resulting from exposure to pesticides [398]. In a study using MPTP (1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine), 3-nitropropionic acid (3-NP), and malonate to induce PD symptoms in mice, Andreassen et al. found that heterozygous MnSOD knockout mice have greater dopamine depletion and larger striatal lesions compared to wildtype mice [401]. "
    [Show abstract] [Hide abstract] ABSTRACT: The mitochondrion is vital for many metabolic pathways in the cell, contributing all or important constituent enzymes for diverse functions such as β-oxidation of fatty acids, the urea cycle, the citric acid cycle, and ATP synthesis. The mitochondrion is also a major site of reactive oxygen species (ROS) production in the cell. Aberrant production of mitochondrial ROS can have dramatic effects on cellular function, in part, due to oxidative modification of key metabolic proteins localized in the mitochondrion. The cell is equipped with myriad antioxidant enzyme systems to combat deleterious ROS production in mitochondria, with the mitochondrial antioxidant enzyme manganese superoxide dismutase (MnSOD) acting as the chief ROS scavenging enzyme in the cell. Factors that affect the expression and/or the activity of MnSOD, resulting in diminished antioxidant capacity of the cell, can have extraordinary consequences on the overall health of the cell by altering mitochondrial metabolic function, leading to the development and progression of numerous diseases. A better understanding of the mechanisms by which MnSOD protects cells from the harmful effects of overproduction of ROS, in particular, the effects of ROS on mitochondrial metabolic enzymes, may contribute to the development of novel treatments for various diseases in which ROS are an important component.
    Full-text · Article · Dec 2011
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