Exposure to pyrethroids may increase the risk of Parkinson’s disease due to interaction with genetics through the immune system.
Pyrethroids are found in most commercial household pesticides. Although they are neurotoxic to insects, they are generally considered safe for human contact by federal authorities.
Genetic variations and pesticide exposure appear to influence the risk of Parkinson’s disease. A new study finds a link between these two risk factors, highlighting the role of the immune response in disease progression.
The findings relate to a class of pesticides called pyrethroids, which are found in most commercial household pesticides and are increasingly used in agriculture as other pesticides are phased out. Although pyrethroids are neurotoxic to insects, federal authorities generally consider them safe for human exposure.
The study is the first to link pyrethroid exposure to genetic risk for Parkinson’s disease and warrants follow-up studies, said co-senior author Malu Tansi, Ph.D., assistant professor of physiology at Emory University School of Medicine.
The genetic variant the team discovered is in the non-coding region of the MHC II (major histocompatibility complex class II) genes, a group of genes that regulate the immune system.
“We didn’t expect to find a specific link to pyrethroids,” Tansey said. “It is known that acute exposure to pyrethroids can cause immune dysfunction, and the molecules they act on can be found in immune cells; We now need to understand more about how long-term exposure affects the immune system and thereby enhances its function.” Risk of Kinson’s disease.”
“There is already strong evidence that brain inflammation or an overactive immune system may contribute to the progression of Parkinson’s disease. “We think what may be happening here is that environmental exposures may alter the immune response in some people, promoting chronic inflammation in the brain.”
For the study, Emory researchers led by Tansey and Jeremy Boss, Ph.D., chair of the Department of Microbiology and Immunology, teamed up with Stuart Factor, Ph.D., director of Emory’s Comprehensive Parkinson’s Disease Center, and Beate Ritz. , MD, University of California, San Francisco. In collaboration with public health researchers at UCLA, Ph.D. The first author of the article is George T. Kannarkat, MD.
UCLA researchers used a California geographic database covering 30 years of pesticide use in agriculture. They determined exposure based on distance (someone’s work and home addresses) but did not measure pesticide levels in the body. Pyrethroids are thought to degrade relatively quickly, especially when exposed to sunlight, with a half-life in soil of days to weeks.
Among 962 subjects from California’s Central Valley, a common MHC II variant combined with above-average exposure to pyrethroid pesticides increased the risk of Parkinson’s disease. The most dangerous form of the gene (individuals carrying two risk alleles) was found in 21% of patients with Parkinson’s disease and 16% of controls.
In this group, exposure to the gene or pyrethroid alone did not significantly increase the risk of Parkinson’s disease, but the combination did. Compared to the average, people who were exposed to pyrethroids and carried the highest risk form of the MHC II gene had a 2.48 times greater risk of developing Parkinson’s disease than those with less exposure and carried the lowest risk form of the gene. risk. Exposure to other types of pesticides, such as organophosphates or paraquat, does not increase risk in the same way.
Larger genetic studies, including Factor and his patients, have previously linked MHC II gene variations to Parkinson’s disease. Surprisingly, the same genetic variant affects the risk of Parkinson’s disease differently in Caucasians/Europeans and Chinese people. MHC II genes vary greatly between individuals; therefore, they play an important role in the selection of organ transplants.
Other experiments have shown that genetic variations associated with Parkinson’s disease are related to immune cell function. Researchers found that among 81 Parkinson’s disease patients and European controls from Emory University, immune cells from people with high-risk MHC II gene variants from the California study showed more MHC molecules.
MHC molecules underlie the process of “antigen presentation” and are the driving force that activates T cells and engages the rest of the immune system. MHC II expression is increased in quiescent cells of Parkinson’s disease patients and healthy controls, but greater response to immune challenge is observed in Parkinson’s disease patients with higher-risk genotypes;
The authors concluded: “Our data suggest that cellular biomarkers, such as MHC II activation, may be more useful than soluble molecules in plasma and cerebrospinal fluid for identifying people at risk of disease or for recruiting patients to participate in trials of immunomodulatory drugs.” ” Test.”
The study was supported by the National Institute of Neurological Disorders and Stroke (R01NS072467, 1P50NS071669, F31NS081830), the National Institute of Environmental Health Sciences (5P01ES016731), the National Institute of General Medical Sciences (GM47310), the Sartain Lanier Family Foundation, and the Michael J. Foxpa Kingson Foundation for Disease Research .
Post time: Jun-04-2024