Age, Genetics Affect PD Risk in Pesticide Exposure

The risk for developing Parkinson's disease that is associated with pesticide exposure appears to be especially high in people who are professionally exposed to the chemicals and those who carry certain polymorphisms for glutathione S-transferase genes, according to data from two new case-control studies.

The studies strengthen the already well-documented association between pesticide exposure and Parkinson's disease (PD) by including a more detailed assessment of exposure to the chemicals for analyzing dose-effect relationships, especially for different classes of insecticides, fungicides, and herbicides, as well as examining the role of genetic traits in determining individual susceptibility to PD.

Dr. Alexis Elbaz of the Institut National de la Santé et de la Recherche Médicale, Paris, and his colleagues conducted extensive in-person interviews about professional exposure to pesticides with 247 patients with PD and 676 matching control patients. All of the participants came from the same French health insurance organization for workers in agriculture and related occupations. The patients with PD had been diagnosed a median of 1.5 years before the study (Ann. Neurol. 2009 [doi:10.1002/ana.21717

Dr. Elbaz and his associates found that for men, the odds of developing PD increased with the number of years of professional use of pesticides. This relationship was stronger for men with PD onset after age 65 years than it was for men with younger onset. Women with pesticide exposure also were significantly more likely to develop PD than were those without exposure.

Of the three broad categories of pesticides that the investigators analyzed–insecticides, fungicides, and herbicides–only insecticide exposure in men was associated with a significantly increased odds of developing PD (odds ratio 2.2). This association followed a dose-effect relationship, which was strongest for older-onset PD patients. In women, only fungicide exposure was associated with significantly increased odds of developing PD (odds ratio 3.5). In multivariate analyses of men overall and of men with older-onset PD, only organochlorine insecticides remained associated with PD after adjusting for other pesticide families that the men had been exposed to.

During 1941-1990, patients with older-onset PD had used organochlorines in each 10-year period more often than their matched controls had, whereas there was no difference in use during the same periods between patients with younger-onset PD and their matched controls. Each control group used organochlorines, as well as insecticides and pesticides, at similar frequencies.

The finding that the association between PD and professional pesticide use was stronger for older males is “consistent with the view that genetic susceptibility plays a stronger role in younger-onset cases, while environmental factors play a stronger role for older-onset cases,” the investigators wrote.

In a separate study, Dr. Ruey-Meei Wu of the department of neurology at National Taiwan University Hospital, Taipei, and her colleagues genotyped 125 patients (69 women) with sporadic idiopathic PD and 162 age- and gender-matched control patients (90 women) from a rural area of southern Taiwan for four glutathione S-transferase (GST) genes (GSTM1, GSTP1, GSTT1, and GSTZ1). Overall, 69 PD patients and 70 control patients were exposed to pesticides (herbicides, insecticides, and fungicides) used in professional farming or gardening. These patients had been exposed to pesticides for a range of 1 to 50 years, Dr. Wu and her colleagues reported at a poster session of the International Congress of Parkinson's Disease and Movement Disorders in Paris.

GST polymorphisms have been reported to reduce the efficiency of the substrate selectivity or stability of the enzymes. In brain tissue, GSTs function as scavengers that eliminate the formation of intracellular free radicals that are generated from the metabolism of drugs, toxins such as pesticides, or xenobiotics. GSTs have the potential to modify a person's susceptibility to developing PD after pesticide exposure by increasing oxidative stress in the brain, leading to the degeneration of dopaminergic neurons, Dr. Wu said in an interview.

Pesticide exposure was an independent risk factor for PD. Only the GSTP1 Val 105 polymorphism, which occurred in about 20% of the patients, significantly increased the risk for the development of PD. This polymorphism raised the odds of developing PD by a factor of 2.2. The risk for PD was greatest among patients who had been exposed to pesticides for more than 35 years.

Those who carried the GSTP1 Val 105 polymorphism and were exposed to pesticides had even higher risk of developing PD. There was a trend for increasing PD risk that became stronger and more significant in pesticide-exposed patients who carried an additional putative high-risk GST genotype.

None of the investigators in either study had any conflicts of interest to declare.

The odds of developing Parkinson's disease rose with the number of years of professional use of pesticides.©LOOK PHOTO/

The risk for developing Parkinson's disease that is associated with pesticide exposure appears to be especially high in people who are professionally exposed to the chemicals and those who carry certain polymorphisms for glutathione S-transferase genes, according to data from two new case-control studies.

The studies strengthen the already well-documented association between pesticide exposure and Parkinson's disease (PD) by including a more detailed assessment of exposure to the chemicals for analyzing dose-effect relationships, especially for different classes of insecticides, fungicides, and herbicides, as well as examining the role of genetic traits in determining individual susceptibility to PD.

Dr. Alexis Elbaz of the Institut National de la Santé et de la Recherche Médicale, Paris, and his colleagues conducted extensive in-person interviews about professional exposure to pesticides with 247 patients with PD and 676 matching control patients. All of the participants came from the same French health insurance organization for workers in agriculture and related occupations. The patients with PD had been diagnosed a median of 1.5 years before the study (Ann. Neurol. 2009 [doi:10.1002/ana.21717

Dr. Elbaz and his associates found that for men, the odds of developing PD increased with the number of years of professional use of pesticides. This relationship was stronger for men with PD onset after age 65 years than it was for men with younger onset. Women with pesticide exposure also were significantly more likely to develop PD than were those without exposure.

Of the three broad categories of pesticides that the investigators analyzed–insecticides, fungicides, and herbicides–only insecticide exposure in men was associated with a significantly increased odds of developing PD (odds ratio 2.2). This association followed a dose-effect relationship, which was strongest for older-onset PD patients. In women, only fungicide exposure was associated with significantly increased odds of developing PD (odds ratio 3.5). In multivariate analyses of men overall and of men with older-onset PD, only organochlorine insecticides remained associated with PD after adjusting for other pesticide families that the men had been exposed to.

During 1941-1990, patients with older-onset PD had used organochlorines in each 10-year period more often than their matched controls had, whereas there was no difference in use during the same periods between patients with younger-onset PD and their matched controls. Each control group used organochlorines, as well as insecticides and pesticides, at similar frequencies.

The finding that the association between PD and professional pesticide use was stronger for older males is “consistent with the view that genetic susceptibility plays a stronger role in younger-onset cases, while environmental factors play a stronger role for older-onset cases,” the investigators wrote.

In a separate study, Dr. Ruey-Meei Wu of the department of neurology at National Taiwan University Hospital, Taipei, and her colleagues genotyped 125 patients (69 women) with sporadic idiopathic PD and 162 age- and gender-matched control patients (90 women) from a rural area of southern Taiwan for four glutathione S-transferase (GST) genes (GSTM1, GSTP1, GSTT1, and GSTZ1). Overall, 69 PD patients and 70 control patients were exposed to pesticides (herbicides, insecticides, and fungicides) used in professional farming or gardening. These patients had been exposed to pesticides for a range of 1 to 50 years, Dr. Wu and her colleagues reported at a poster session of the International Congress of Parkinson's Disease and Movement Disorders in Paris.

GST polymorphisms have been reported to reduce the efficiency of the substrate selectivity or stability of the enzymes. In brain tissue, GSTs function as scavengers that eliminate the formation of intracellular free radicals that are generated from the metabolism of drugs, toxins such as pesticides, or xenobiotics. GSTs have the potential to modify a person's susceptibility to developing PD after pesticide exposure by increasing oxidative stress in the brain, leading to the degeneration of dopaminergic neurons, Dr. Wu said in an interview.

Pesticide exposure was an independent risk factor for PD. Only the GSTP1 Val 105 polymorphism, which occurred in about 20% of the patients, significantly increased the risk for the development of PD. This polymorphism raised the odds of developing PD by a factor of 2.2. The risk for PD was greatest among patients who had been exposed to pesticides for more than 35 years.

Those who carried the GSTP1 Val 105 polymorphism and were exposed to pesticides had even higher risk of developing PD. There was a trend for increasing PD risk that became stronger and more significant in pesticide-exposed patients who carried an additional putative high-risk GST genotype.

None of the investigators in either study had any conflicts of interest to declare.

The odds of developing Parkinson's disease rose with the number of years of professional use of pesticides.©LOOK PHOTO/

The risk for developing Parkinson's disease that is associated with pesticide exposure appears to be especially high in people who are professionally exposed to the chemicals and those who carry certain polymorphisms for glutathione S-transferase genes, according to data from two new case-control studies.

The studies strengthen the already well-documented association between pesticide exposure and Parkinson's disease (PD) by including a more detailed assessment of exposure to the chemicals for analyzing dose-effect relationships, especially for different classes of insecticides, fungicides, and herbicides, as well as examining the role of genetic traits in determining individual susceptibility to PD.

Dr. Alexis Elbaz of the Institut National de la Santé et de la Recherche Médicale, Paris, and his colleagues conducted extensive in-person interviews about professional exposure to pesticides with 247 patients with PD and 676 matching control patients. All of the participants came from the same French health insurance organization for workers in agriculture and related occupations. The patients with PD had been diagnosed a median of 1.5 years before the study (Ann. Neurol. 2009 [doi:10.1002/ana.21717

Dr. Elbaz and his associates found that for men, the odds of developing PD increased with the number of years of professional use of pesticides. This relationship was stronger for men with PD onset after age 65 years than it was for men with younger onset. Women with pesticide exposure also were significantly more likely to develop PD than were those without exposure.

Of the three broad categories of pesticides that the investigators analyzed–insecticides, fungicides, and herbicides–only insecticide exposure in men was associated with a significantly increased odds of developing PD (odds ratio 2.2). This association followed a dose-effect relationship, which was strongest for older-onset PD patients. In women, only fungicide exposure was associated with significantly increased odds of developing PD (odds ratio 3.5). In multivariate analyses of men overall and of men with older-onset PD, only organochlorine insecticides remained associated with PD after adjusting for other pesticide families that the men had been exposed to.

During 1941-1990, patients with older-onset PD had used organochlorines in each 10-year period more often than their matched controls had, whereas there was no difference in use during the same periods between patients with younger-onset PD and their matched controls. Each control group used organochlorines, as well as insecticides and pesticides, at similar frequencies.

The finding that the association between PD and professional pesticide use was stronger for older males is “consistent with the view that genetic susceptibility plays a stronger role in younger-onset cases, while environmental factors play a stronger role for older-onset cases,” the investigators wrote.

In a separate study, Dr. Ruey-Meei Wu of the department of neurology at National Taiwan University Hospital, Taipei, and her colleagues genotyped 125 patients (69 women) with sporadic idiopathic PD and 162 age- and gender-matched control patients (90 women) from a rural area of southern Taiwan for four glutathione S-transferase (GST) genes (GSTM1, GSTP1, GSTT1, and GSTZ1). Overall, 69 PD patients and 70 control patients were exposed to pesticides (herbicides, insecticides, and fungicides) used in professional farming or gardening. These patients had been exposed to pesticides for a range of 1 to 50 years, Dr. Wu and her colleagues reported at a poster session of the International Congress of Parkinson's Disease and Movement Disorders in Paris.

GST polymorphisms have been reported to reduce the efficiency of the substrate selectivity or stability of the enzymes. In brain tissue, GSTs function as scavengers that eliminate the formation of intracellular free radicals that are generated from the metabolism of drugs, toxins such as pesticides, or xenobiotics. GSTs have the potential to modify a person's susceptibility to developing PD after pesticide exposure by increasing oxidative stress in the brain, leading to the degeneration of dopaminergic neurons, Dr. Wu said in an interview.

Pesticide exposure was an independent risk factor for PD. Only the GSTP1 Val 105 polymorphism, which occurred in about 20% of the patients, significantly increased the risk for the development of PD. This polymorphism raised the odds of developing PD by a factor of 2.2. The risk for PD was greatest among patients who had been exposed to pesticides for more than 35 years.

Those who carried the GSTP1 Val 105 polymorphism and were exposed to pesticides had even higher risk of developing PD. There was a trend for increasing PD risk that became stronger and more significant in pesticide-exposed patients who carried an additional putative high-risk GST genotype.

None of the investigators in either study had any conflicts of interest to declare.

The odds of developing Parkinson's disease rose with the number of years of professional use of pesticides.©LOOK PHOTO/