An Association between Idiopathic Parkinson's Disease and Polymorphisms of Phase II Detoxification Enzymes: Glutathione S-Transferase M1 and Quinone Oxidoreductase 1 and 2

Harada, Shoji; Fujii, Chieko; Hayashi, Atsushi; Ohkoshi, Norio

doi:10.1006/bbrc.2001.5868

Cited by 119 publications

(84 citation statements)

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“…prevent dopaminergic degeneration through their direct antioxidant activity against various reactive metabolites of chemical toxicants produced by phase I enzyme metabolism [8,23,17]. GSTs may also serve a neuroprotective function by facilitating the elimination of endogenous toxins, including the toxic o-quinones of dopamine, from the cell [1].…”

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confidence: 99%

Glutathione S-transferase mu, omega, pi, and theta class variants and smoking in Parkinson's disease

Wahner

Glatt

Bronstein

et al. 2007

Neuroscience Letters

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GSTs are a family of inducible phase II enzymes that may play a neuroprotective role in Parkinson's disease (PD). GSTs may also modify PD risk by metabolizing compounds in cigarettes, as cigarette smoking is generally found to be associated with a decrease in PD risk. Using a population-based case control study design, we examined polymorphisms of the mu, omega, pi, and theta classes of GST to elucidate the main effects and smoking-GST interactions on PD risk. From three rural California counties, we recruited 289 incident idiopathic PD cases, clinically confirmed by our study neurologist, and 270 population controls, marginally matched by age, gender, and race.We assessed main gene polymorphism associations and evaluated interactions between smoking and GST polymorphisms as departures from a multiplicative scale adjusting for age, gender, and race. We also restricted analyses to Caucasian subjects to address the potential for population stratification (n=235 cases, 220 controls).Among Caucasians, we observed a risk reduction in subjects carrying at least one variant allele for GSTO1 (OR= 0.68, 95% CI: 0.47-0.98) and also GSTO2 (OR= 0.64, 95% CI: 0.44-0.93); both genes were in strong linkage disequilibrium. No main gene effects were observed for the remaining polymorphisms. We noted a multiplicative interaction between ever having smoked regularly and GSTO1 (OR interaction = 0.55, 95% CI: 0.33-0.92) and GSTO2 (OR interaction = 0.54, 95% CI: 0.32-0.90). Results were similar when combining all races. These findings and the paucity of similar studies suggests a need for further inquiry into the association between GSTs, smoking, and PD risk. KeywordsGene-environment interaction; Glutathione-S-transferase; Parkinson's disease; SmokingThe death of dopaminergic neurons in the midbrain is a characteristic feature of Parkinson's disease (PD). Glutathione-S-transferases (GSTs), a family of inducible phase II enzymes with cytoprotective properties, are hypothesized to protect against neurodegeneration. GSTs may Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. . The small number of studies that previously explored interactions between GST gene polymorphisms and smoking in PD were inconclusive and subject to limitations in study design and sample size [3,4,13]. Here we present the first population-based case control study to examine the interaction between several GST polymorphisms and smoking in PD. NIH Public AccessWe concentrated on polymorphisms in four of eight classes of cytoplasmic mammalian GSTs (mu, omega, pi, theta). These classes and their respective gene polymorphi...

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confidence: 99%

Glutathione S-transferase mu, omega, pi, and theta class variants and smoking in Parkinson's disease

Wahner

Glatt

Bronstein

et al. 2007

Neuroscience Letters

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“…Genotyping for this gene was performed by a combination of two types of polymerase chain reaction (PCR) amplification as reported previously (Harada et al, 2001a;2001b). The first type of PCR was used for the detection of a non-deletion allele with the appropriate primers:…”

Section: Methodsmentioning

confidence: 99%

“…GSTM1 has an entire gene deletion polymorphism and its enzymatic activity is classified into three grades, i.e., a highly active genotype (homozygous non-deletion alleles; NN), a moderately active genotype (heterozygous non-deletion alleles; DN), and a null genotype (homozygous deletion alleles; DD) (McLellan et al, 1997). Recently, it has been reported that the frequency of D allele of GSTM1 gene in the patients with schizophrenia was significantly (p=0.0075) higher than that of normal controls, suggesting that GSTM1 gene may be associated with an increased susceptibility to schizophrenia (Harada et al, 2001a). Thus, it seems that differences in the GSTM1 genotype may contribute to the development of MAP abuse.…”

Section: Introductionmentioning

confidence: 99%

Association between the glutathione S‐transferase M1 gene deletion and female methamphetamine abusers

Koizumi

Hashimoto

Kumakiri

et al. 2003

American J of Med Genetics Pt B

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Several lines of evidence suggest that increased generation of auto-oxidized dopamine (DA) o-quinone is associated with the neurotoxicity of methamphetamine (MAP) in the brain, and that, as a cellular defenses against DA-derived quinines, glutathione S-transferase (GST) detoxifies auto-oxidized DA o-quinone in the brain. GSTM1 of the mu-class of GSTs catalyzes reaction between glutathione and catecholamine o-quinones under physiological conditions. This study was undertaken to investigate the role of the GSTM1 gene deletion polymorphism in the neuropathology of MAP abuse. One hundred and fifty-seven MAP abusers and 200 healthy comparison subjects were tested for a genetic polymorphism of GSTM1. The difference in the frequency of deletion (D)/ non-deletion (N) alleles between the female abusers and female controls was close to statistical significance (p=0.071), although thee was no statistical difference (p=0.651) between male abusers and male controls. Furthermore, the number of female abusers with deletion alleles was significantly (p=0.007, odds ratio: 2.77, 95% CI 1.30-5.89) higher than that of male abusers with deletion alleles. These findings suggest that GSTM1 gene deletion may contribute to a vulnerability to MAP abuse in female subjects, but not in male subjects.

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“…95 The remaining four studies did not confirm these results, and did not find any association between GST polymorphisms and the risk of PD. [96][97][98][99] The variability of these findings precludes a definitive conclusion regarding the association of GST polymorphism with IPD risk. …”

Section: Glutathione S-transferasesmentioning

confidence: 99%

“…Of the four that focused on polymorphisms of NAT2 in chromosomes 8p21.3-23.1, all reported a higher frequency of the slow acetylator genotype in PD 81,98,100 or in young-onset PD. 101 However, the remaining studies, which investigated three mutant alleles M1, M2, and M3 of NAT-2, did not find any differences in allelic frequencies or genotypic distributions between patients with IPD and age-matched controls from the Netherlands, 102 Europe, 103 and the US.…”

Section: N-acetyl Transferasementioning

confidence: 99%

Polymorphism in candidate genes: implications for the risk and treatment of idiopathic Parkinson's disease

et al. 2004

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Idiopathic Parkinson's disease (IPD) is a progressive neurodegenerative disorder for which no restorative or neuroprotective therapy is available. Interest has recently been directed to association studies on polymorphisms of various genes, mainly those related to dopamine metabolism and transport, and their effect on response to PD, which includes primarily levodopa and dopaminomimetics. Approximately 15-20% of patients with PD do not respond to levodopa, and the majority of those who do respond develop adverse fluctuations in motor response, primarily levodopa-induced dyskinesias. This review summarizes the influence of polymorphisms in various genes on the relative risk of IPD and on levodopa efficacy. It focuses on the importance of well-designed polymorphism studies that include large samples of patients with IPD and tightly matched controls and use identical methodologies. Valid data on such polymorphisms might increase the efficacy of levodopa, decrease its side effects, and reduce the occurrence of levodopa-induced dyskinesias. They might also provide a novel diagnostic tool for PD.

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An Association between Idiopathic Parkinson's Disease and Polymorphisms of Phase II Detoxification Enzymes: Glutathione S-Transferase M1 and Quinone Oxidoreductase 1 and 2

Cited by 119 publications

References 26 publications

Glutathione S-transferase mu, omega, pi, and theta class variants and smoking in Parkinson's disease

Glutathione S-transferase mu, omega, pi, and theta class variants and smoking in Parkinson's disease

Association between the glutathione S‐transferase M1 gene deletion and female methamphetamine abusers

Polymorphism in candidate genes: implications for the risk and treatment of idiopathic Parkinson's disease

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