Pesticides, genetic vulnerability tied to higher Parkinson's risk

By Anne Harding

NEW YORK (Reuters Health) - Exposure to pesticides that block aldehyde dehydrogenase (ALDH) is associated with a higher risk of Parkinson's disease (PD), new findings show.

And individuals with common variants in the ALDH2 gene were at even greater risk when exposed to these pesticides, Dr. Beate Ritz of the Fielding School of Public Health at UCLA in Los Angeles and her colleagues found.

"Now that we know that these agents are inhibiting this pathway and putting people at risk, we should probably be thinking about regulations to keep these agents away from humans so they are not exposed," Dr. Ritz told Reuters Health.

ALDH detoxifies a damaging dopamine metabolite known as DOPAL, Dr. Ritz and her team note in their February 4 report online in Neurology, so "its inhibition offers a potential mechanism for the preferential loss of dopaminergic neurons in PD."

To investigate further, Dr. Ritz and her team developed an ex vivo assay to identify whether pesticides inhibited neuronal ALDH activity. They tested 26 pesticides, and found 11 that did inhibit ALDH, including maneb, ziram, triflumizole, captan, folpet, and dieldrin.

The investigators then estimated exposure to eight of the ALDH-inhibiting pesticides among 360 PD patients and 816 healthy controls participating in the Parkinson's Environment & Genes study. The study participants lived in California's Central Valley, an agricultural region with heavy pesticide use. The investigators also identified seven ALDH2 haplotypes among the study participants, dividing them into two clades.

Exposure to each of the eight pesticides was associated with an increased PD risk, which increased with greater exposure. People exposed to an ALDH-inhibiting pesticide at both work and home were 65 percent to 600 percent more likely to have PD. The more pesticides a person was exposed to, the greater the risk.

Individuals who were homozygous for clade 1 ALDH2 variants were not at increased risk of PD when exposed to any level of ALDH-inhibiting pesticides. However, those with at least one copy from clade 2 (about one-third of the study participants) were at a two- to five-fold increased risk of PD when exposed to the pesticides.

"The people that we actually determined to have this exposure wouldn't even know that they did," Dr. Ritz said. "It's ambient exposure from living in these communities where the farming industry uses these agents." Therefore, she added, it would be impractical to advise people to move in order to reduce their PD risk. Instead, Dr. Ritz said, regulations should be considered that would create buffer zones between where the agricultural chemicals are used and where people live and work - or ban these substances altogether.

"What we need to prevent is people from being exposed whether they know it or not," she added. "It's not a personal responsibility, it's really a social responsibility about being vigilant about what kinds of toxins we're putting out in the environment that really shouldn't be used near humans."

Some of the pesticides tested, she noted, did not inhibit ALDH activity. "That's what makes these results so exciting, because they are quite specific," Dr. Ritz said. "We have come a long way from saying that every pesticide is neurotoxic and every pesticide causes Parkinson's."

The findings also point toward new strategies for treating or even preventing PD, she added. "This pathway is important, so hopefully if we can manipulate this pathway, maybe help it along in some people, you would also be able to prevent Parkinson's."

Dr. Freya Kamel, who studies pesticides and Parkinson's risk at the National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina, reviewed the study for Reuters Health. "It's a well done and important study," she said. "I think it opens up some new avenues of research and new possibilities for thinking about strategies to prevent or slow the progression of Parkinson's disease. If you could slow the progression, it would make a big difference to the lives of people who are affected."

SOURCE: http://bit.ly/1kZYWpi

Neurology 2014.

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