Nullity of GSTT1/GSTM1 related to pesticides is associated with Parkinson's disease

Pinhel, Marcela Augusta de Souza; Sado, Caroline L.; Longo, Gabriela dos Santos; Gregório, Michele Lima; Amorim, Gisele S.; Florim, Greiciane Maria da Silva; Mazeti, Camila Montoro; Martins, Denise Poltronieri; Oliveira, Fábio de Nazaré; Nakazone, Marcelo Arruda; Tognola, Waldir Antônio; Souza, Dorotéia Rossi Silva

doi:10.1590/0004-282x20130076

Cited by 27 publications

(8 citation statements)

References 25 publications

(31 reference statements)

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“…This is an agreement with previous report of Kubiszeski et al [9] in Cuiabá population (50% and 32%) and Rocha et al [10] in Amazônia population. Other studies in the Brazilian population from Bahia, performed by Rocha et al [10] and Pinhel et al [11] in the population from São Paulo confirm our findings in the Goiânia population. GSTM1 and GSTT1 enzymes metabolize several precarcinogens, drugs, constituents of tobacco smoke and solvents to reactive metabolites which ultimately lead to DNA or protein damage [12].…”

Section: Discussionsupporting

confidence: 90%

Investigation of Gluthatione S-Transferase Variants in a Healthy Population in Goiânia-Go

Pereira¹,

Bérgamo²,

Reis³

et al. 2018

Adv Tech Biol Med

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The study was performed according approved by the ethics committee of Federal University of Goias (approval CEP: 895.552). In the current survey, 100 patients (35M/65F) of both genders and aged 18-90 (M: 30.2) years old considered healthy and practicing physical activity 2 to 3 times a week, were enrolled after receiving their informed consent. Sample collection and DNA analyzes Peripheral blood (5mL) was collected in EDTA vacutainer tubes from all participating individuals after obtaining their written consent. Until the DNA extraction blood DNA collections was store a-20°C. Genomic DNA extraction was performed from whole blood using a Purelink Genomic DNA Kit (Invitrogen, Life Technologies Inc.; USA) and the concentration was measured using a NanoDrop™ 2000/2000c Spectrophotometers (Thermo Scientific, USA).

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Section: Discussionsupporting

confidence: 90%

Investigation of Gluthatione S-Transferase Variants in a Healthy Population in Goiânia-Go

Pereira¹,

Bérgamo²,

Reis³

et al. 2018

Adv Tech Biol Med

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“…Alterations in the expression of GST isoenzymes in brain have been connected to neurological disorders including Alzheimeŕs disease [142], epilepsy [143] and Parkinsońs disease [144,145]. However, it remains to be elucidated whether the expression or activity of astrocytic GSTs are altered in such diseases.…”

Section: Conjugation Of Gsh With Endogenous Compounds and Xenobioticsmentioning

confidence: 99%

Glutathione-Dependent Detoxification Processes in Astrocytes

et al. 2014

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Astrocytes have a pivotal role in brain as partners of neurons in homeostatic and metabolic processes. Astrocytes also protect other types of brain cells against the toxicity of reactive oxygen species and are considered as first line of defence against the toxic potential of xenobiotics. A key component in many of the astrocytic detoxification processes is the tripeptide glutathione (GSH) which serves as electron donor in the GSH peroxidase-catalyzed reduction of peroxides. In addition, GSH is substrate in the detoxification of xenobiotics and endogenous compounds by GSH-S-transferases which generate GSH conjugates that are efficiently exported from the cells by multidrug resistance proteins. Moreover, GSH reacts with the reactive endogenous carbonyls methylglyoxal and formaldehyde to intermediates which are substrates of detoxifying enzymes. In this article we will review the current knowledge on the GSH metabolism of astrocytes with a special emphasis on GSH-dependent detoxification processes.

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“…Furthermore, other genes re1ated to PD, such as APOE, GSTs and LRRK2 (PARK8), also showed no difference between patients and controls in this population 20,21,22,23 . On the other hand, mutations in the genes GIGYF (PARK11), ATP13A2 (PARK9) and GBA were associated with PD 6 .…”

Section: Discussionmentioning

confidence: 71%

Alpha-synuclein A53T mutation is not frequent on a sample of Brazilian Parkinson’s disease patients

Longo

Pinhel

Gregório

et al. 2015

Arq. Neuro-Psiquiatr.

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Parkinson's disease (PD) is one of the major degenerative disorders, affecting 2% of the population over 65 years and up to 4% in people over 85 years 1 . In Brazil, statistics show that the incidence of PD amounts to 150/200 cases per 100,000 inhabitants 2 . Most cases of PD are idiopathic 3 . However, in approximately 5%-10% of the cases, there is a genetic component with both dominant and recessive inheritance patterns 3 . The chromosomal loci linked to the familial forms of PD are termed PARK1-13. These loci include six autosomal dominant genes [PARK 1or PARK 4 (alpha synuclein -SNCA), PARK 3 (Lewy bodies), PARK 5 (ubiquitin carboxyl-terminal esterase L1 -UCHL1), PARK 8 (leucine-rich repeat kinase 2 -LRRK2) and PARK13 (HTRA serine peptidase 2 -HTRA2)], 4 recessives genes [PARK 2 ABSTRACT Introduction:The pathogenesis of Parkinson's disease (PD) involves both genetic susceptibility and environmental factors, with focus on the mutation in the alpha-synuclein gene (SNCA). Objective: To analyse the polymorphism SNCA-A53T in patients with familial PD (FPD) and sporadic PD (SPD). Method: A total of 294 individuals were studied, regardless of sex and with mixed ethnicity. The study group with 154 patients with PD, and the control group included 140 individuals without PD. The genotyping of SNCA-A53T was performed by PCR/RFLP. Significance level was p < 0.05. Results: Among all patients, 37 (24%) had FPD and 117 (75.9%) had SPD. The absence of SNCA-A53T mutation was observed in all individuals. Conclusion: SPD is notably observed in patients. However, the SNCA-A53T mutation was absent in all individuals, which does not differ controls from patients. This fact should be confirmed in a Brazilian study case with a more numerous and older population. Keywords:Parkinson's disease, alpha-synuclein, mutation. RESUMO Introdução:A patogênese da doença de Parkinson (DP) envolve fatores ambientais e suscetibilidade genética, destacando-se a mutação de alfa-sinucleína (SNCA.) Objetivos: Analisar a variante genética SNCA-A53T em pacientes com DP familiar (DPF) e DP esporádica (DPE). Método: Foram estudados 294 indivíduos, independente de sexo, com etnia miscigenada, sendo 154 com DP e 140 sem a doença (grupo controle). A genotipagem de SNCA-A53T foi realizada por PCR/RFLP. Nível de significância para p < 0,05. Resultados: Entre os pacientes, 37(24%) tinham DPF e 117 (75,9%) DPE. A ausência da mutação SNCA-A53T em todos os indivíduos. Conclusão: DPE é destacada entre os pacientes, no entanto a mutação SNCA-A53T ausente em todos os indivíduos, não diferenciando os grupo controle e pacientes, o que deve ser confirmado em população brasileira, considerando uma ampla casuística, além da ancestralidade.Palavras-chave: doença de Parkinson, alfa sinucleína, mutação.

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Nullity of GSTT1/GSTM1 related to pesticides is associated with Parkinson's disease

Cited by 27 publications

References 25 publications

Investigation of Gluthatione S-Transferase Variants in a Healthy Population in Goiânia-Go

Investigation of Gluthatione S-Transferase Variants in a Healthy Population in Goiânia-Go

Glutathione-Dependent Detoxification Processes in Astrocytes

Alpha-synuclein A53T mutation is not frequent on a sample of Brazilian Parkinson’s disease patients

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