Saliva DNA may aid in Parkinson’s diagnosis, risk assessment
Researchers say genetic analysis could serve as noninvasive test method
Genetic analysis of saliva may offer a noninvasive way to assess the risk of developing Parkinson’s disease, according to a saliva-based DNA study led by researchers at the University of the Basque Country (EHU) in Spain.
The scientists found that molecular markers in saliva can reflect whole-body disease processes, suggesting the potential for early detection not only of Parkinson’s but also of cancer, heart disease, diabetes, and other neurological conditions.
“Saliva is one of the most accessible biological fluids but it is still underutilised in clinical practice,” José Ramón Bilbao, PhD, professor of medical genetics at the EHU and the study’s senior author, said in a university news story. “Our results show that molecular markers present in saliva can reflect systemic [whole-body] pathological processes beyond the oral cavity.”
The study, “Saliva as a potential diagnostic medium: DNA methylation biomarkers for disorders beyond the oral cavity,” was published in npj Genomic Medicine.
Although the findings warrant further study and validation, they could help with the development of saliva-based tools for diagnosing and assessing disease risk, the researchers said.
DNA and disease risk
“[T]his work opens the door to developing saliva-based testing that could in the future be used for the early detection of diseases or for monitoring treatments, without the need to extract blood or perform other invasive procedures,” said Alba Hernangómez-Laderas, a PhD student at EHU and lead author of the study.
To support these efforts and advance new research, the researchers created what they said is the largest public database of saliva-based genetic data, available through an open-access platform.
Parkinson’s causes include environmental and genetic factors. Some 5%-10% of cases can be traced to mutations in a single gene. However, many other genetic variations can influence disease risk without causing Parkinson’s.
Single nucleotide polymorphisms (SNPs) are changes in individual DNA building blocks that can influence gene expression, or which genes are turned on or off and when. This may occur through DNA methylation, a process in which cells add a chemical compound, called a methyl group, to specific parts of the gene. Methyl groups influence gene expression without altering the underlying DNA sequence.
Certain expression and methylation patterns might contribute to the risk of developing a certain disorder, so analyzing SNPs could be useful in diagnosing Parkinson’s and assessing its risk. However, it can be challenging to obtain samples of tissue likely to show these markers.
Blood samples are one option, but saliva samples have advantages over blood, according to the researchers. “Compared to other tissues, saliva offers unparalleled accessibility for sample collection, does not require specialized medical equipment or personnel, and multiple samples can be collected over a short period of time,” they wrote.
To identify possible genetic markers of disease risk, the team collected saliva samples from 381 adult volunteers of European ancestry. They analyzed DNA sequences, methyl groups, and markers of genetic expression.
The researchers identified two types of genetic markers that could be influenced by SNPs’ variations in DNA. The first type, called mSites, are spots in the genome where genetic changes may affect DNA methylation. The second type, known as eGenes, are genes whose activity levels can be influenced by genetic variations.
The team compared these markers to data from previous studies on genetic risk factors for Parkinson’s and other diseases. This helped them pinpoint risk-related signals that could be detected in saliva. “The most significant implication of this work is that saliva harbors independent and disease-specific regulatory signals that can be leveraged for non-invasive diagnostics,” the researchers wrote.
In Parkinson’s disease, they found three mSites in saliva that may be linked to disease risk. When the data were analyzed by sex, even more potential markers appeared: 16 mSites in women and 10 in men. While no eGenes were linked to Parkinson’s overall, the team did identify one sex-specific eGene in men and another in women.
These findings suggest that saliva could be used to identify people at higher risk for Parkinson’s and potentially other diseases. In fact, the researchers also found sex-specific markers related to other conditions.
Data also showed how DNA methylation and gene expression can work together. An mSite called cg23202277 was found to influence the expression of a nearby gene called RPS26P8. In people with Parkinson’s, lower methylation at this site and lower expression of the gene were both associated with higher disease risk, pointing to a possible role for this gene in the disease.
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