Genetic Makeup Determines Parkinson's Risk From Pesticide Use
February 5, 2014

Genetic Makeup Determines Parkinson’s Risk From Pesticide Use

Rebekah Eliason for – Your Universe Online

In the past, studies have shown that pesticides can cause an increased risk for the development of Parkinson’s disease. Recently, UCLA researchers have discovered that amount of risk varies with a person’s individual genetic makeup. People with a specific genetic variant and are living in extreme pesticide-exposed areas have an increased likelihood of developing the disease by two- to six-fold.

Previously, the UCLA team found that Parkinson’s was linked with the pesticide benomyl, which is a fungicide that was banned by the U.S. Environmental Protection Agency (EPA).

In that study, the researchers discovered that benomyl inhibits the enzyme aldehyde dehydrogenase (ALDH). This vital enzyme protects dopamine cells by converting highly toxic aldehydes into less toxic molecules. When this enzyme is inhibited, it is much more likely for Parkinson’s to develop.

For this study, the UCLA team tested several pesticides and discovered that eleven others inhibit ALDH and also cause an increased risk of Parkinson’s.

Jeff Bronstein, professor of neurology and director of movement disorders at UCLA, said that these pesticides inhibit the enzyme at significantly lower levels than those which are currently being used.

Bronstein noted that the team also found that people with a common genetic variant of the ALDH2 gene are particularly sensitive to the effects of ALDH-inhibiting pesticides, and were two to six times more likely to develop Parkinson's than those without the variant when exposed to these pesticides.

“We were very surprised that so many pesticides inhibited ALDH and at quite low concentrations, concentrations that were way below what was needed for the pesticides to do their job,” Bronstein said. “These pesticides are pretty ubiquitous, and can be found on our food supply and are used in parks and golf courses and in pest control inside buildings and homes. So this significantly broadens the number of people at risk.”

In the study, researchers compared 360 patients with Parkinson’s from three different heavily agricultural Central California counties to 816 people living in the same areas without Parkinson’s. Based on information from the California Department of Pesticide Regulation, the analysis was focused on those with surrounding exposure to pesticides both at home and at work.

Previously in the PNAS study, Bronstein’s team established the mechanism which increases the risk for Parkinson’s. As a person is exposed to pesticides, a sequence of cellular events prevents ALDH from regulating the naturally occurring toxin DOPAL. If ALDH fails to effectively detoxify DOPAL, the toxin accumulates in the brain and causes damage to neurons that increase the risk of developing Parkinson’s.

Beate Ritz, a professor of epidemiology at the Fielding School of Public Health at UCLA, said, “ALDH inhibition appears to be an important mechanism by which these environmental toxins contribute to Parkinson's pathogenesis, especially in genetically vulnerable individuals. This suggests several potential interventions to reduce Parkinson's occurrence or to slow its progression.”

Researchers developed a lab test for this study that determined which pesticides inhibit ALDH. The team discovered that when participants in the study with the genetic variant of the ALDH gene were exposed to pesticides, they had an increased risk for developing the disease. Just having the variant alone, however, did not increase risk of the disease, Bronstein said

“This report provides evidence for the relevance of ALDH inhibition in Parkinson's disease pathogenesis, identifies pesticides that should be avoided to reduce the risk of developing Parkinson's disease and suggests that therapies modulating ALDH enzyme activity or otherwise eliminating toxic aldehydes should be developed and tested to potentially reduce Parkinson's disease occurrence or slow its progression particularly for patients exposed to pesticides,” the study reports.

This study appeared February 5, 2014 in the online issue of Neurology.