Pesticides plus genetics increase risk of Parkinson's Disease

Parkinson’s disease is the most common neurodegenerative movement disorder in the US. Low levels of the nerve-to-nerve signal transmitter dopamine in the brain cause the disease.

Dopamine transporters are molecules that carry dopamine to specific nerve cells. The dopamine transporter gene controls the amount of transporter molecules available. Changes to the gene are thought to affect the amount of transporter molecules and dopamine among nerve cells in the brain.

Variation in the dopamine transporter gene is common. About 75 percent of the population has at least one genetic change and almost 40 percent have at least two genetic differences.

Several researchers have hypothesized that changes in the number of alleles – up to four – in the gene would render an individual more susceptible to developing Parkinson’s disease. However, few studies have been able to test this hypothesis.

Common symptoms for people with Parkinson's disease include tremors, muscle stiffness, slowness and lack of balance. These symptoms become worse with time.

The disease affects approximately 1 percent of all people over the age of 65. Rates of Parkinson’s disease appear higher among farmers and rural residents, leading to speculation that pesticides might play a role in development of the disease.

In laboratory mice, two pesticides that affect dopamine levels – paraquat and maneb – have been shown to cause Parkinson’s-like symptoms (Barlowa et al. 2004). The effect is strongest when animals are exposed to these two compounds in combination (Thiruchelvam et al. 2002).

Recent studies now indicate that exposure to these two pesticides may also increase risk of Parkinson’s in humans. Exposure to one compound alone does not appear to confer increased risk. It appears that the combination of the two compounds is necessary (Costello et al. 2009).

Paraquat and maneb are among the top 25 most commonly used agricultural pesticides in California. More than one million pounds of each compound is applied annually in the state.

Paraquat is commonly used to kill weeds in agricultural fields, while maneb is used to control fungi in soil. Both pesticides are often used on the same food crops, including potatoes, beans and tomatoes. Exposure to both compounds at the same time is not unusual.

What did they do?

The investigators enrolled 324 people with newly diagnosed Parkinson’s disease and 334 healthy people, as controls, living in California’s agricultural Central Valley.

All the homes that an individual had lived in since 1974 were mapped and compared with state records that track all agricultural pesticide use in California. The authors were able to identify people who had lived within 500 yards of fields where the pesticides maneb and paraquat had been used at any time during the previous 35 years.

Individuals were also interviewed to determine whether they had ever been exposed to pesticides through their jobs.

DNA samples were extracted from blood samples or cheek swabs to detect genetic variability in the dopamine transporter gene.

What did they find?

People with one susceptible allele who lived near fields where maneb and paraquat were used had a three-fold increased risk of developing Parkinson’s disease.

People who had two or more susceptible genetic variants (alleles) had almost a 5-fold increase in risk.

Importantly, people who were genetically susceptible but had no pesticide exposure showed no increased risk.

end of excerpt