Pesticides plus genetics increase risk of Parkinson's disease.

May 14, 2009

Ritz B, A Manthripragada, S Costello, S Lincoln, M Farrer, M Cockburn, J Bronstein. 2009. Dopamine transporter genetic variants and pesticides in Parkinson's disease. Environmental Health Perspectives doi:10.1289/ehp.0800277.




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Exposure to commonly used agricultural pesticides may increase the risk of developing Parkinson’s disease, particularly among people who have certain gene types. The degenerative nerve disease can develop when dopamine levels in the brain are lower than normal. Without pesticide exposures, susceptible gene variants alone were not sufficient to increase risk. The increased risk to Parkinson's required both susceptible genes and pesticide exposure.


 

 

 

Context

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.

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. 

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.

What does it mean?

Parkinson’s disease, like many diseases, appears to be caused by a complex interaction of genetic and environmental factors.

This study is the second in people to demonstrate a synergy between the pesticides paraquat and maneb and the dopamine transporter gene. It validates a previous study by different researchers (Kelada et al. 2006). 

This study suggests that individual’s with a particular genetic make-up may be particularly sensitive to the neurodegenerative effects of certain pesticides.

Homes and other residential exposures, not work-related exposures, were the focus of the study. People living near farm fields where the pesticides are used can be exposed to the chemicals via wind and dust.

Because both genetic susceptibility and use of maneb and paraquat are common, this could have important implications for residents of agricultural communities.

Resources

Barlowa, BK, EK Richfielda, DACory-Slechtab, M Thiruchelvamb. 2004. A fetal risk factor for Parkinson's disease. Developmental Neuroscience 26:11-23.

Costello, S, M Cockburn, J Bronstein, X Zhang and B Ritz. 2009. Parkinson's disease and residential exposure to maneb and paraquat from agricultural applications in the Central Valley of California. American Journal of Epidemiology 169: 919-926.

Kelada, SN, H Checkoway, SL Kardia, CS Carlson, P Costa-Mallen, DL Eaton, J Firestone, KM Powers, PD Swanson, GM Franklin, WT Longstreth, Jr, T-S Weller, Z Afsharinejad and LG Costa. 2006. 5' and 3' region variability in the dopamine transporter gene (SLC6A3), pesticide exposure and Parkinson's disease risk: a hypothesis generating study. Human Molecular Genetics 15(20):3055-3062.

Parkinson's disease information page. National Institute of Nurological Disease and Stroke. National Institutes of Health.

Thiruchelvam, M, EK Richfield, BM Goodman, RB Baggs and DA Cory-Slechta. 2002. Developmental exposure to the pesticides paraquat and maneb and the Parkinson’s disease phenotype. NeuroToxicology 23:621-633.

 

 

 

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