Parkinson's disease is a neurodegenerative disorder that impairs movement, and happens when cells in a region of the brain called the basal ganglia become dysfunctional or begin to die. These cells normally generate an important neurotransmitter called dopamine. There is also a loss of a portion of some neurons that produce another important neurotransmitter called norepinephrine. Millions of people are affected by the disease.
Scientists have now identified specific genetic patterns in the blood cells of patients with Parkinson's. These patterns involve methylation, a chemical modification that can significantly alter gene expression, but does not change the sequence of the genome. These DNA methylation patterns may be useful in the diagnosis of Parkinson's, or as a biomarker of disease progression. The findings have been reported in Annals of Neurology.
There are a variety of environmental factors that have been recently linked to an increase in the risk of Parkinson's, such as exposure to pesticides or a particular chemical in dry-cleaning called trichloroethylene (TCE).
Scientists are still trying to learn more about how these environmental factors may leads to Parkinson's disease. In this study, the researchers analyzed methylation patterns in DNA isolated from blood samples from 196 Parkinson's disease patients and 86 unaffected individuals as part of the the Parkinson's Progression Markers Initiative (PPMI) study.
"DNA methylation in some ways serves as a memory of prior environmental exposures that ultimately alter methylation signatures in our cells and body," noted study leader Paulina Gonzalez-Latapi, MD, MS, an assistant professor at Northwestern University.
Genome-wide methylation data and gene expression data from RNA-sequencing was obtained over a period of three years for each individual, from white blood cells and platelets (and red blood cells, though most of these cells do not carry DNA). This effort revealed 75 genes whose expression changed, and also had different methylation patterns in Parkinson's patients compared to unaffected people.
The CYP2E1 gene had consistent methylation changes from the start and end of the three-year study period. The protein produced by this gene is known to be related to the metabolism of certain substances such as pesticides.
"It's a significant step towards unraveling the complex interactions at play in Parkinson's disease and could pave the way for pinpointing potential biomarkers for early detection and progression," noted Gonzalez-Latapi.
The researchers are also interested in how DNA methylation may be relevant to individuals who are at risk of Parkinson's disease but who have not yet developed symptoms of the illness, or whether it methylation patterns are connected to exposure to certain Parkinson's-related chemicals.
Sources: Northwestern University, Annals of Neurology