Pesticides and the Genetic Link
The central valley of California is a major producer of all the fruits and vegetables consumed, not just in the United States, but all over the world. Production of huge yearly crops depends upon serious planning and management, including the use of herbicides and pesticides. So three counties in this major agricultural region (Fresno, Kern and Tulare) became a very appropriate laboratory to study the effects of pesticides for Jeff M. Bronstein, MD, PhD, professor of neurology and director of Movement Disorders at the Geffen School of Medicine, University of California at Los Angeles.
His team developed a study, The Parkinson’s Environment and Genes (PEG) Study that recruited subjects from three of the most agricultural counties in the state of California. In the laboratory they found that many pesticides inhibit aldehyde dehydrogenase (ALDH) activity and this inhibition is also associated with risk of developing PARKINSON’S DISEASE. So the team tested 26 different pesticides and found only four structural classes of ALDH inhibiting pesticides that contribute to the risk of developing PARKINSON’S DISEASE. .
All humans carry a gene for ALDH, but not all humans exposed to pesticides develop PARKINSON’S DISEASE Interestingly, some people carry polymorphisms (slightly different versions) of the ALDH gene, and if they have no exposure to pesticides they do not develop PARKINSON’S DISEASE. Also, the study suggests that only about 6 per cent of people exposed to ALDH inhibiting pesticides actually develop PARKINSON’S DISEASE.
However, if a person carries a polymorphism for the ALDH gene, the, exposure to ALDH inhibiting pesticides increases the risk of developing PARKINSON’S DISEASE proportionately to the number of pesticides to which they are exposed. If a person was exposed to one, there was risk, but if they were exposed to six, the risk would be 6 times higher, and most people exposed to pesticides in the agricultural community are exposed to many. A six fold greater risk is enormous. The study also looked at whether a person was exposed only at work or only at home or at both and found much higher correlations when the exposure was at both work and home.
Inhibition of ALDH is thought to occur thru a chemical, dihydroxyphenylacetaldehyde (DOPAL), which is a dopamine derivative. And therein lies a potential target to lower the risk through inhibiting the enzyme that makes DOPAL. Dr. Bronstein notes that there are already drugs on the market that can protect against pesticide poisoning, but finding the 6 percent of the population that is at risk would be difficult to accomplish.
This study is an early but important step in showing mechanism of action between genetics and the environment in PARKINSON’S DISEASE and also to the number of exposures. It helps explain why the connection between pesticides and PARKINSON’S DISEASE which has long been suspected but was so difficult to prove. This study should bring more interest and research into this area to protect the people that are exposed to pesticides and to perhaps help develop less toxic pesticides that do not inhibit ALDH. It also seriously enforces the attention to regulation and safety issues for storing and handling pesticides as well as the methods of application.
J.M. Bronstein et al; How Pesticides May Boost Parkinson’s Risk; Neurology, 2014; 82:419-126
Review by Marcia McCall