Parkinson's disease is thought to be secondary to the presence of  neurotoxins, and pesticides have been implicated as possible causative agents.

 

 

Subject:   Your "Registered" POISONS Thought to Cause Parkinson's Disease--
Date:      Sat, 05 Aug 2000 17:21:41 -0400
From:        Stephen Tvedten <steve@getipm.com>
Organization:     Get Set Inc. (www.getipm.com)

To:     Paul Helliker <phelliker@cdpr.ca.gov>
          Director, State of California, Department of Pesticide Regulation 

Dear Mr. Helliker,  I thought you might like to read a Medical article from The Lancet - Issue: Oct 24, 1998 entitled: Parkinson's disease, pesticides, and glutathione transferase polymorphisms. (Early Reports). 

Summary - Background: Parkinson's disease is thought to be secondary to the presence of  neurotoxins, and pesticides have been implicated as possible causative agents. Glutathione transferases (GST) metabolise xenobiotics, including pesticides. Therefore, we investigated the role of GST polymorphisms in the pathogenesis of idiopathic Parkinson's disease. 

Methods: We genotyped by PCR polymorphisms in four GST classes (GSTM1, GSTT1, GSTP1, and GSTZ1) in 95 Parkinson's disease patients and 95 controls. We asked all patients for information about pesticide exposure. 

Findings: The distribution of the GSTP1 genotypes differed significantly between patients and controls who had been exposed to pesticides (controls vs patients: AA 14 [54%] of 26 vs seven [18%] of 39; AB 11 [42%] of 26 vs 22 [56%] of 39; BB 1 [4%] of 26 vs six [15%] of 39; AC 0 vs four [10%] of 39, p=0.009). No association was found with any of the other GST polymorphisms. 
Pesticide exposure and a positive family history were risk factors for Parkinson's disease.  

Interpretation: GSTP1-1, which is expressed in the blood-brain barrier, may influence response to neurotoxins and explain the susceptibility of some people to the parkinsonism-inducing effects of pesticides.  

Introduction.  Many studies suggest that Parkinson's disease is more common among people  who report exposure to pesticides.1,2 There are case reports of acute parkinsonism after exposure to paraquat3 and organophosphate insecticides.4 Not all people exposed to pesticides, however, develop Parkinson's disease.  Reports suggest that some people may have a genetic susceptibility to Parkinson's disease mediated by enzymes involved in the disposition of pesticides and other putative neurotoxins, for example, cytochrome P450 2D6 and N-acetyltransferase-2.5,6  

Glutathione transferases (GSTs) are a ubiquitous group of detoxification enzymes involved in the metabolism of pesticides7 and other toxins.8 The activity of GST has been reported to be normal in the brains of people with Parkinson's disease.9 Only studies of single substrates have been reported,  and in human beings there are several classes of GST with different substrate specificities and tissue distributions.10 Several GST polymorphisms have been identified.11-15 The polymorphisms of the GSTM1 and GSTT1 loci arise from the complete deletion of each gene15,16 and can affect substantially the metabolism of some substances, such as trans-stilbene oxide (GSTM1)16 and  the alkylhalides (GSTT1).15 The polymorphisms at the GSTP1 and GSTZ1 loci result in aminoacid substitutions that have more subtle effects. There is good evidence that the polymorphisms of GSTP1 effect substrate selectivity and stability.17,18  

These polymorphisms and their effects on substrate selectivity make the GSTs plausible candidate genes for susceptibility to Parkinson's disease. We investigated the association between Parkinson's disease pesticide exposure and polymorphisms in four GST genes.  ...  

The remainder of the article (3-4) pages can be read at the following site:   
http://www.findarticles.com/cf_0/m0833/1998_Oct_24/53146710/p1/article.jhtml 

Respectfully,  Stephen L. Tvedten

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