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.]