Researchers ID 3 genes linked to disease activity in Parkinson’s
Genes could serve as diagnostic biomarkers for disease if validated
Researchers in China have identified three genes — GPX2, CR1, and ZNF556 — with increased activity in people with Parkinson’s disease that could play a role in its development.
If validated in future studies, these genes could ultimately serve as disease biomarkers to facilitate Parkinson’s diagnoses.
“Our study identifies GPX2, CR1, and ZNF556 [as] critical to the pathogenesis [development] of PD [Parkinson’s disease] … providing new insights into the genetic landscape of this complex disorder,” the researchers wrote. “These findings contribute to the growing body of evidence supporting the role of genetic factors in PD and underscore the potential of using multigene panels for improving PD diagnosis.”
According to the researchers, such work will allow scientists to “predict an individual’s risk of developing PD with increasing accuracy.”
The study, “Exploring and validating key genetic biomarkers for diagnosis of Parkinson’s disease,” was published in the journal Brain Research Bulletin.
Aim is to develop better diagnostic tools to screen for Parkinson’s
Parkinson’s disease is a complex neurodegenerative disorder believed to arise from a combination of environmental and genetic risk factors.
While a minority of patients have familial Parkinson’s, in which the condition is inherited in families when certain genetic mutations are passed down, most have a sporadic form of disease that’s not considered to be directly inherited.
Nonetheless, scientists have now come to understand that a variety of genetic mutations, along with environmental factors, may still collectively influence disease risk for people with sporadic Parkinson’s.
To that end, better understanding the genetic basis of the neurodegenerative disease will help scientists develop new diagnostic tools to screen people for Parkinson’s. Gene mutations linked to the disease have the potential to serve as biomarkers, the researchers noted.
“As a neurodegenerative disease, PD is primarily diagnosed based on clinical symptoms; however, by the time characteristic motor symptoms appear, substantial disease progression has often already taken place,” the researchers wrote.
The search for reliable [Parkinson’s disease] biomarkers has garnered significant attention due to the critical need for early and accurate diagnostic tools that can improve patient outcomes.
This means that treatment often is delayed relative to an earlier diagnosis.
“The search for reliable PD biomarkers has garnered significant attention due to the critical need for early and accurate diagnostic tools that can improve patient outcomes,” the researchers wrote.
To contribute toward that goal, the scientists examined genetic data from Parkinson’s patients and healthy people, aiming to identify genes that might be involved in the disease’s development.
The team used different publicly available genetic datasets — including ones comprising blood or brain tissue samples — and identified genes with altered activity, or expression, in people with Parkinson’s.
GPX2, CR1, and ZNF556 linked to significantly higher gene activity
The results showed 13 genes with significantly higher activity in Parkinson’s patients across the datasets. Computer algorithms were then able to narrow this list down to three that seemed most closely linked to the neurodegenerative condition. These were GPX2, CR1, and ZNF556.
To confirm the findings, the scientists screened blood samples from another group of 60 Parkinson’s patients and 60 healthy people, again finding that these three genes had elevated expression in Parkinson’s.
Interestingly, GPX2 and CR1 had higher expression in the subgroup of patients with early-stage disease compared with those with more advanced disease.
In a cell model of Parkinson’s disease, all three genes had increased expression compared with healthy cells, consistent with the observations in patient samples.
Given their possible association with Parkinson’s, the scientists believe the genes could have diagnostic value. The team found that predictive models based on the expression of each gene in blood samples had a moderate ability to distinguish Parkinson’s samples from healthy ones.
The diagnostic accuracy was increased when all three genes were considered together, the scientists found.
“This observation supports the emerging consensus that a multibiomarker approach may be more effective than relying on single-gene markers for PD diagnosis,” the researchers wrote.
More studies will be needed to firmly establish the role of each of these genes in Parkinson’s, but all have been linked to processes implicated in the disease, including inflammation and oxidative stress, a type of cellular damage.
“Future research should prioritize larger validation studies and explore the functional roles of these biomarkers to fully realize their clinical potential,” the team concluded.
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