Pesticide exposure on southwestern Taiwanese with MnSOD and NQO1 polymorphisms is associated with increased risk of Parkinson's disease
Yuan Ze University, Taoyuan City, Taiwan, Taiwan Clinica Chimica Acta
(Impact Factor: 2.82).
03/2007; 378(1-2):136-41. DOI: 10.1016/j.cca.2006.11.006
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.
Available from: Roel Vermeulen
- "The search in Embase and Medline yielded 883 publications, of which 52 publications met the inclusion criteria. We excluded 3 publications (Fong et al. 2005; Menegon et al. 1998; Smargiassi et al. 1998) where the study population had been included in subsequent publications (De Palma et al. 1998; Fong et al. 2007; McCann et al. 1998). Lastly, one study (Taylor et al. 1999) was excluded because the reported data showed risk per year of pesticide exposure, which was not comparable with reported risk ratios of other studies. "
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ABSTRACT: Previous systematic reviews have indicated that pesticide exposure is possibly associated with Parkinson disease (PD). However, considerable heterogeneity has been observed in study results.
We aimed at providing an update of the literature published on PD and exposure to pesticides by performing a systematic review and meta-analysis. In addition, we investigated whether methodological differences between studies could explain the heterogeneity in study results.
We identified studies through a systematic literature search. We calculated summary risk ratios (sRRs) for pesticide exposure and subcategories using random effects meta-analyses and investigated sources of heterogeneity by meta-regression and stratified analyses.
Thirty-nine case-control studies, four cohort studies, and three cross-sectional studies were identified. An sRR of 1.62 [95% confidence interval (CI): 1.40, 1.88] for pesticide exposure (ever vs. never) was found. Summary estimates for subclasses of pesticides indicated a positive association with herbicides and insecticides, but not with fungicides. Heterogeneity in individual study results was not related to study design, source of control population, adjustment of results for potential confounders, or geographical area. However, results were suggestive for heterogeneity related to differences in the exposure assessment. Job title-based exposure assignment resulted in a higher sRR (2.5; 95% CI: 1.5, 4.1) than did assignment based on self-reported exposure (e.g., for self-reported ever/never exposure, sRR = 1.5; 95% CI: 1.3, 1.8).
This review affirms the evidence that exposure to herbicides and insecticides increase the risk of PD. Future studies should focus on more objective and improved methods of pesticide exposure assessment.
Available from: Janelle Drouin-Ouellet
- "Furthermore, a significant association was reported between the combined MnSOD/NQO1 variant genotype among subjects exposed to pesticides and increased PD risk (OR = 4.09; 95% CI 1.34-10.64, p = 0.0052) (Fong et al. 2007). "
Available from: Hara P Misra
- "The unique role of NQO1 in detoxification of electrophilic quinone molecules and ROS suggests that this phase 2 enzyme may play an important part in protecting against dopaminergic neurodegeneration in PD patients. In this context, polymorphism of NQO1 has been suggested to be associated with an increased risk of developing PD (Fong et al., 2007). In addition to NQO1, GSH is also capable of reacting with quinone molecules as well as ROS to attenuate dopamine or 6-OHDA-induced cytotoxicity (Shimizu et al., 2002). "
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ABSTRACT: Evidence suggests oxidative and electrophilic stress as a major factor contributing to the neuronal cell death in neurodegenerative disorders, especially Parkinson's disease. Consistent with this concept, administration of exogenous antioxidants has been shown to be protective against oxidative/electrophilic neurodegeneration. However, whether induction of endogenous antioxidants and phase 2 enzymes by the unique chemoprotectant, 3H-1,2-dithiole-3-thione (D3T) in neuronal cells also affords protection against oxidative and electrophilic neurocytotoxicity has not been carefully investigated. In this study, we showed that incubation of SH-SY5Y neuroblastoma cells or primary human neurons with micromolar concentrations (10-100 microM) of D3T for 24 h resulted in significant increases in the levels of reduced glutathione (GSH) and NAD(P)H:quinone oxidoreductase 1 (NQO1), two crucial cellular defenses against oxidative and electrophilic stress. D3T treatment also caused increases in mRNA expression of gamma-glutamylcysteine ligase catalytic subunit and NQO1 in SH-SY5Y cells. In addition, D3T treatment of the neuronal cells also resulted in a marked elevation of GSH content in the mitochondrial compartment. To determine the protective effects of the D3T-induced cellular defenses on neurotoxicant-elicited cell injury, SH-SY5Y cells were pretreated with D3T for 24 h and then exposed to dopamine, 6-hydroxydopamine (6-OHDA), 4-hydroxy-2-nonenal (HNE), or H2O2, agents that are known to be involved in neuron degeneration. We observed that D3T-pretreatment of SH-SY5Y cells led to significant protection against the cytotoxicity elicited by the above neurotoxicants. Similar neurocytoprotective effects of D3T-pretreatment were also observed in primary human neurons exposed to 6-OHDA or HNE. Taken together, this study demonstrates that D3T potently induces neuronal cellular GSH and NQO1 as well as mitochondrial GSH, and that such upregulated endogenous defenses are accompanied by increased resistance to oxidative and electrophilic neurocytotoxicity.
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