Herbicide exposure modifies
            <i>GSTP1</i>
            haplotype association to Parkinson onset age

Wilk, J. B.; Tobin, JE; Suchowersky, Oksana; Shill, HA; Klein, Christine; Wooten, G. Frederick; Lew, Michael S.; Mark, MH; Guttman, Mark; Watts, R. L.; Singer, Carlos; Jh, Growdon; Latourelle, Jeanne C.; Saint-Hilaire, Marie H.; DeStefano, A. L.; Prakash, Ranjana; Williamson, Sally; Berg, C. T. Van Den; Sun, Mei; Goldwurm, Stefano; Pezzoli, Gianni; Racette, B. A.; Perlmutter, J. S.; Parsian, Abbas; Baker, KB; Giroux, Monique; Litvan, Irene; Pramstaller, Peter P.; Nicholson, Garth A.; Burn, David J.; Chinnery, Patrick F.; Vieregge, P.; Jt, Slevin; Cambi, Franca; MacDonald, ME; Jf, Gusella; Myers, Richard H.; Golbe, L. I.

doi:10.1212/01.wnl.0000249149.22407.d1

Cited by 45 publications

(30 citation statements)

References 27 publications

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“…27 More recently, an interaction of herbicide exposures and a GSTP1 haplotype on age at onset of PD was reported. 28 However, neither of those observations has been independently replicated. Interactions of paraoxonase and dopamine transporter genes and pesticides and PD also await replication.…”

Section: Resultsmentioning

confidence: 99%

α-Synuclein, pesticides, and Parkinson disease

et al. 2008

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Section: Resultsmentioning

confidence: 99%

α-Synuclein, pesticides, and Parkinson disease

et al. 2008

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“…Interestingly, findings consistent with a gene-environment interaction have already been reported for other candidate genes: For instance, a polymorphism in the CYP2D6 gene, which results in a 'poor metabolizer' phenotype of the encoded detoxifying enzyme, altered the risk for PD when exposed to pesticides [7]. Further, polymorphisms in the GSTP1 gene, encoding another detoxifying enzyme, seem to influence the risk of PD after pesticide exposure [17] and the age at onset of familial PD in conjunction with herbicide exposure [29].…”

Section: Discussionmentioning

confidence: 96%

MDR1 variants and risk of Parkinson disease

et al. 2009

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The multidrug resistance protein 1 (MDR1 or ABCB1) gene encodes a P-glycoprotein that protects the brain against neurotoxicants. Certain MDR1 genetic variants are known to compromise the function of this transporter and may thus be associated with Parkinson disease (PD). We therefore conducted a large case-control study investigating the potential relationship between MDR1 variants and PD. We determined the frequency of three MDR1 variants in 599 European PD patients and controls and further stratified the population by ethnicity, age at onset, and exposure to pesticides. We detected no relevant association in either the entire sample, or when separately investigating by ethnic origin or age at onset. However, the distribution of c.3435C/T differed significantly between PD patients exposed to pesticides compared to those non-exposed (odds ratio=4.74; confidence interval=[1.009; 22.306]); p=0.047), suggesting that common MDR1 variants might influence the risk to develop PD in conjunction with exposure to pesticides.

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“…However, in this study, the wild genotype (I/I) presented association with familial PD. Studies involving GSTP1 polymorphisms and familial PD are scarce 9 , making population comparisons difficult.…”

Section: Discussionmentioning

confidence: 99%

“…There is an association between GSTP1 genotypes and PD in individuals exposed to pesticides, which shows that the GSTP1 possibly affects the nigrostriatal response to neurotoxins 7,8 . Also, GSTP1 polymorphisms can influence onset age for PD 4,9 . On the other hand, there are controversies surrounding the risks or protection, involving GSTP1, tobacco use and PD 10 .…”

mentioning

confidence: 99%

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

Longo

Pinhel

Sado

et al. 2013

Arq. Neuro-Psiquiatr.

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Parkinson's disease (PD) is the second most common neurodegenerative disorder, showing high prevalence in elderly patients also in Brazil, with an incidence of 150/200 cases per 100,000 inhabitants ABSTRACT Objective:This study aimed to analyze the frequency of GSTP1-Alw26I polymorphism and to estimate its association with toxic substances in Parkinson's disease (PD). Methods: A study group with 154 patients -subdivided into familial and sporadic PD groups -and 158 elderly individuals without the disease (control group) were evaluated. GSTP1-Alw26I polymorphism was analyzed by polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP). Results: Patients were significantly more exposed to pesticides compared with the control group (p=0.0004), and the heterozygote genotype associated to exposure to pesticides also prevailed in patients (p=0.0001). Wild homozygote genotype was related to tobacco use (p=0.043) and alcoholism (p=0.033) in familial PD patients. Conclusion: Exposure to pesticides is associated to PD, whose effect can be enhanced when combined with the heterozygote genotype of GSTP1-Alw26I. Also, large genetic and environmental studies considering tobacco use, alcoholism, GSTP1 and PD are necessary to confirm our findings.Key words: glutathione transferase, genetic polymorphism, Parkinson disease, xenobiotics. RESUMOObjetivo: Analisar a frequência do polimorfismo GSTP1-Alw26I, assim como estimar sua associação com substâncias tóxicas na doença de Parkinson (DP). Métodos: A casuística avaliada foi composta por um grupo de estudo, com 154 pacientes, subdivididos em DP familial e esporádica, e outro com 158 idosos sem a doença (grupo controle). O polimorfismo GSTP1-Alw26I foi analisado por reação em cadeia da polimerase/polimorfismo de comprimento do fragmento de restrição (PCR/RFLP). Resultados: Os pacientes foram significativamente mais expostos a pesticidas, comparados com o grupo controle (p=0,0004), e o genótipo heterozigoto associado a exposição a pesticidas também prevaleceu nos pacientes (p=0,0001). O genótipo homozigoto selvagem apresentou relação com tabagismo (p=0,043) e etilismo (p=0,033) em pacientes com DP familial. Desse modo, a exposição a pesticidas está associada à DP, cujo efeito pode ser potencializado quando combinado ao genótipo heterozigoto de GSTP1-Alw26I. Estudos genético-ambientais envolvendo tabagismo, etilismo, GSTP1 e DP devem ser realizados em casuísticas numerosas, confirmando essa associação.Palavras-Chave: glutationa transferase, polimorfismo genético, doença de Parkinson, xenobióticos.

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Herbicide exposure modifies GSTP1 haplotype association to Parkinson onset age

Abstract: Herbicide exposure may be an effect modifier of the relation between glutathione S-transferase pi gene polymorphisms and onset age in familial PD.

Cited by 45 publications

References 27 publications

α-Synuclein, pesticides, and Parkinson disease

α-Synuclein, pesticides, and Parkinson disease

MDR1 variants and risk of Parkinson disease

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

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