Monday, November 25, 2013

The link between pesticides and genetics and Parkinson's disease

A really fascinating article by Lauren Wolf on the link between pesticides and Parkinson's. To me, this is the key passage:
Still, “the vast majority of us are not getting Parkinson’s, and the vast majority of people who work with pesticides don’t get Parkinson’s,” Goldman says. “So there’s obviously something else at play.” 
That “something,” today’s scientists believe, is genetic susceptibility. Along with Tanner and Kamel, Goldman explored this gene-environment interaction recently by surveying a group of male farmers. The researchers genotyped the participants’ DNA to determine which subjects had mutations in a gene coding for glutathione S-transferase T1. This type of enzyme is responsible for cleansing cells of foreign substances such as pesticides and protecting against oxidative stress. 
Men who were exposed to paraquat and who had nonfunctional glutathione S-transferase were 11 times more likely to have Parkinson’s disease than nonexposed men who had functional enzymes (Mov. Disord. 2012, DOI: 10.1002/mds.25216). 
Another recent study examined the association of pesticides, Parkinson’s, and mutations to a protein pump called P-glycoprotein. This macromolecule sits on cells lining blood vessels in the brain, defending a person’s gray matter by pushing out molecular intruders. 
Agricultural workers in France who were exposed to organochlorine insecticides and who had gene mutations affecting P-glycoprotein’s performance were three to seven times more likely to have Parkinson’s than those who weren’t exposed (Arch. Neurol. 2010, DOI: 10.1001/archneurol.2010.101).
I am always looking for the mechanism behind chemical/epidemiological studies. Genetic variation in how we deal with xenobiotics makes sense to me; when I say to my non-chemist friends, "you have a liver and it does its job well", there's something to the thought that well, different people have different livers.

[This will also lend itself to lots of #chemophobia-tinged scares, where members of the general public may/will diagnose themselves with inefficient/insufficient CYP450, etc. Can't win 'em all.]

5 comments:

  1. "different people have different livers" - I've been on development teams for several drugs whose metabolites were equally / more active than the parent compound, so trying to get a handle on dosing into cirrhotic / hepatic impairment populations can get confusing very fast. But this is another great example of how many layers can exist when trying to answer a relatively straightforward question, and why so often the answer is "some times". As helpful as that is.

    Also, for your post script, let's not forget that grapefruit juice and St. John's Wort are known effective CYP inhibitors. So using their logic, fruit and herbal remedies cause Parkinson's.

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  2. What a terrible title for an article by C&E News. It is entirely inflammatory and for a periodical produced by an organization that is supposed to advocate chemistry, it is entirely self-defeating to stoke the fires of chemophobia. Pesticides should always be continuously examined for safety, efficacy, and selectivity, however a title that makes blanket statements that ALL pesticides are LINKED to PARKINSON'S is irresponsible.

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  3. Have to agreee wtih Anon. @ 11:09 PM. The title is extremely inflammatory. The article itself was ok, but seriously, they just begging CNN to pick up on this title and run rampant with it. As someone who works in an agrochemical research lab, this is the kind of stuff that makes me hesitate before telling non-chemists what I do for a living.

    Since they were on the subject, I was also surprised to see the paraquat-suicide connection left out. Paraquat is a nasty molecule, and its unfortunately making a comeback due to widespread herbicide resistant weeds.

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    Replies
    1. First of all, I should make clear that the title of this post: "The link between pesticides and genetics and Parkinson's disease" is mine. Lauren Wolf's article is titled "The Pesticide Connection", which is fairly anodyne, consider the contents.

      I'm willing to take responsibility for criticism for my title, which is more than a little vague.

      Do you (CC) have a problem with my title, or hers?

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    2. I was actually talking about the title of C&EN cover: "Pesticides and Parkinsons" with the giant picture of paraquat destroying someone's neurons. Your title mentions the genetic connection, so its a bit more specific and less of an eyeball grabber. I suppose the point of the cover is to get the reader interested in the article inside, but it still seems a little like something you'd see on a major news website and not in a technical publication. I can just envision people seeing a title like that and thinking "oh no! pesticides cause parkinsons? Add that to the list of horrible things the chemical industry is hiding from us. GET ME TO THE NEAREST WHOLE FOODS STORE NOW!!!!" (not that theres anything wrong with whole foods....they have great cookies).

      Anyway, it just seems like "pesticide" is such a buzz-word these days for getting people up in arms about GMO's and the nasty, nasty chemical industry that they should have come up with something else, but in reality, the article really is about pesticides and parkinsons so it is a technically sound title.

      I think I just contradicted myself, but whatever.

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