Exposure to pesticides and heterozygote genotype of GSTP1-Alw26I are associated to Parkinson's disease

Longo, G.; Pinhel, Marcela Augusta de Souza; Sado, Caroline L.; Gregório, Michele Lima; Amorim, Gisele S.; Florim, Greiciane S.; Mazeti, Camila Montoro; Martins, Denise Poltronieri; Oliveira, F M O Fernanda Matos E; Tognola, Waldir Antônio; Nakazone, Marcelo Arruda; Souza, Dorotéia Rossi Silva

doi:10.1590/0004-282x20130060

Cited by 13 publications

(6 citation statements)

References 27 publications

(67 reference statements)

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“…Interestingly, Longo et al . (2013) recently reported an interaction between heterozygosity for the GSTP1 Ile105Val polymorphism and exposure to pesticides in relation to Parkinson’s disease (Longo et al, 2013). Our results provide further evidence in support of the role of the GSTP1 Ile/Val genotype in susceptibility to a complex disease.…”

Section: Discussionmentioning

confidence: 99%

Interaction between GSTT1 and GSTP1 allele variants as a risk modulating-factor for autism spectrum disorders

Rahbar

Samms‐Vaughan

et al. 2015

Research in Autism Spectrum Disorders

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We investigated the role of glutathione S-transferase (GST) genes in Autism Spectrum Disorder (ASD). We used data from 111 pairs of age- and sex-matched ASD cases and typically developing (TD) controls between 2–8 years of age from Jamaica to investigate the role of GST pi 1 (GSTP1), GST theta 1 (GSTT1), and GST mu 1 (GSTM1) polymorphisms in susceptibility to ASD. In univariable conditional logistic regression models we did not observe significant associations between ASD status and GSTT1, GSTM1, or GSTP1 genotype (all P > 0.15). However, in multivariable conditional logistic regression models, we identified a significant interaction between GSTP1 and GSTT1 in relation to ASD. Specifically, in children heterozygous for the GSTP1 Ile105Val polymorphism, the odds of ASD was significantly higher in those with the null GSTT1 genotype than those with the other genotypes [Matched Odds Ratio (MOR) = 2.97, 95% CI (1.09, 8.01), P = 0.03]. Replication in other populations is warranted.

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Section: Discussionmentioning

confidence: 99%

Interaction between GSTT1 and GSTP1 allele variants as a risk modulating-factor for autism spectrum disorders

Rahbar

Samms‐Vaughan

et al. 2015

Research in Autism Spectrum Disorders

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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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“…A future clinical use of 8-MOP as GST inhibitor must take these information into account. Associations between GSTP1 polymorphism (and activity) and other pathological conditions, mainly neurodegenerative diseases, like multiple sclerosis (Alexoudi et al, 2014), Parkinson's disease (Longo et al, 2013) and essential tremor (Martínez et al, 2008), could suggest side effects of inhibition of GST activity, but, in the other hand, they also increase the potential therapeutic scope of this prototype.…”

Section: Discussionmentioning

confidence: 99%

8-Methoxypsoralen is a competitive inhibitor of glutathione S-transferase P1-1

Oliveira

Farias

Teles

et al. 2014

Front. Cell. Neurosci.

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The blood-brain barrier (BBB) is known to protect healthy brain cells from potentially dangerous chemical agents, but there are many evidences supporting the idea that this protective action is extended to tumor cells. Since the process of angiogenesis in brain tumors leads to BBB breakdown, biochemical characteristics of the BBB seem to be more relevant than physical barriers to protect tumor cells from chemotherapy. In fact, a number of resistance related factors were already demonstrated to be component of both BBB and tumor cells. The enzyme glutathione S-transferases (GST) detoxify electrophilic xenobiotics and endogenous secondary metabolites formed during oxidative stress. A role has been attributed to GST in the resistance of cancer cells to chemotherapeutic agents. This study characterized 8-methoxypsoralen (8-MOP) as a human GST P1-1 (hGST P1-1) inhibitor. To identify and characterize the potential inhibitory activity of 8-MOP, we studied the enzyme kinetics of the conjugation of 1-chloro-2,4-dinitrobenzene (CDNB) with GSH catalyzed by hGST P1-1. We report here that 8-MOP competitively inhibited hGST P1-1 relative to CDNB, but there was an uncompetitive inhibition relative to GSH. Chromatographic analyses suggest that 8-MOP is not a substrate. Molecular docking simulations suggest that 8-MOP binds to the active site, but its position prevents the GSH conjugation. Thus, we conclude that 8-MOP is a promising prototype for new GST inhibitors pharmacologically useful in the treatment of neurodegenerative disorders and the resistance of cancer to chemotherapy.

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Exposure to pesticides and heterozygote genotype of GSTP1-Alw26I are associated to Parkinson's disease

Cited by 13 publications

References 27 publications

Interaction between GSTT1 and GSTP1 allele variants as a risk modulating-factor for autism spectrum disorders

Interaction between GSTT1 and GSTP1 allele variants as a risk modulating-factor for autism spectrum disorders

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

8-Methoxypsoralen is a competitive inhibitor of glutathione S-transferase P1-1

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