Parkinson's disease: the simultaneous presence of several rare genetic variants increases the risk of the disease. Twenty-six genes have been identified, sixteen of which are associated with the disease for the first time. The study was conducted by the Institute of Genetics and Biophysics "Adriano Buzzati Traverso" of the Naples-based National Research Council (Italian acronym CNR-IGB) and the IRCCS Neuromed Mediterranean Neurological Institute (Italian: Istituto Neurologico Mediterraneo Neuromed) and was published in 'Molecular Neurodegeneration'.
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Research resulting from the collaboration between the IRCCS Neuromed and CNR-IGB has shown that some rare genetic variants, if simultaneously present, may play an important role in significantly increasing the risk of developing Parkinson's disease.
The study, published in the scientific journal Molecular Neurodegeneration, examined the genetic data of two types of patients: those belonging to families in which Parkinson's disease recurs and those in which the disease had appeared without any family history ("sporadic" cases). In addition, the authors further investigated gene expression (the process of transcribing genetic information into functional proteins) in both human tissue and animal models. Five of the genes studied were found to be particularly expressed in dopaminergic neurons of the substantia nigra, whose degeneration is the main cause of Parkinson's disease.
This is the largest genetic study carried out on Italian Parkinson's disease patients using state-of-the-art sequencing methods. "We were able to identify variants related to the risk of Parkinson's disease in twenty-six genes, sixteen of which had not previously been associated with the disease. And we were also able to find that most of these genes are involved in pathways that are important for the functionality of the dopaminergic pathways, the degeneration of which leads to the development of the disease", says Alessandro Gialluisi, researcher at the Department of Epidemiology and Prevention at Neuromed, and the study's main author.
An important study finding is that the variants examined may have a kind of cumulative effect. "The simultaneous presence of two or more of these rare variants was found to be associated with an increased probability of developing Parkinson's in 20% of patients. We can speak of a growing 'load' of mutations that, in the future, could lead us to assess the risk of disease precisely through the identification of the number of harmful variants present in a person's DNA," explains Teresa Esposito, researcher at CNR-IGB, head of Neuromed's CNR Laboratory at Neuromed, and second study author.
"These results appear promising with a view to perfecting molecular diagnostic techniques aimed at identifying high-risk individuals at an early stage. Further studies will of course be needed to increase the number of patients who can be diagnosed and to understand and develop potential therapeutic approaches, first and foremost those based on pharmacological developments and regenerative medicine. What we can imagine for the near future is a genetic test that takes into account the load of harmful variants in an individual's genome," concludes Antonio Simeone, CNR-IGB Director. "This could open up important possibilities for launching population screening and, therefore, improving the early diagnosis of a disease that develops over time, and in which symptoms only appear when patients have already lost 50% of their dopaminergic neurons, which are the most involved in Parkinson's".
1. Press release. Parkinson's disease: the simultaneous presence of some rare genetic variants increases the risk of the disease. CNR press office. 21/06/2021
2. Gialluisi A, Reccia MG, Modugno N, Nutile T, Lombardi A, Di Giovannantonio LG, Pietracupa S, Ruggiero D, Scala S, Gambardella S; International Parkinson's Disease Genomics Consortium (IPDGC), Iacoviello L, Gianfrancesco F, Acampora D, D'Esposito M, Simeone A, Ciullo M, Esposito T. Identification of sixteen novel candidate genes for late onset Parkinson's disease. Mol Neurodegener. 2021 Jun 21;16(1):35. doi: 10.1186/s13024-021-00455-2. PMID: 34148545; PMCID: PMC8215754.