Common Gene Variation May Predict Parkinson’s Severity and Progression, Study Reports

Researchers found a genetic variation, known as the GG genotype, that identifies those Parkinson’s disease (PD) patients more likely to have slower disease progression — evidenced through tremors — and lower levels of alpha-synuclein, a protein linked to the disease. The findings have implications in disease diagnosis and treatment strategies, and were recently presented at the 68th Annual Meeting of American Academy of Neurology in Vancouver, Canada.

Clinical evidence suggests that tremors seen as the initial or dominant Parkinson’s symptom, as opposed to balance and walking problems, point to a slower disease progression and lower risk of dementia onset.

Researchers at the Perelman School of Medicine at the University of Pennsylvania investigated single nucleotide polymorphisms (SNPs), genetic variations among the population that, when occurring within a gene or regulatory region near a gene, may affect its function with pathological consequences.

The GG genotype, a relatively common SNP near the alpha-synuclein (SNCA) gene, was found to be a predictor of disease severity.

Genotypes in a total of 251 PD patients were studied, with the focus on 10 PD-associated genetic variations and their influence on patients’ symptoms. Results revealed that 39 of the patients who had the GG genotype were more likely to have tremors, as opposed to balance and walking problems, slower physical disease progression, and lower levels of alpha-synuclein in the brain, the major component of Lewy bodies, a hallmark of PD that greatly contributes to neuronal death. The researchers performed the same analysis in another 559 patients at three other clinical sites in the U.S., finding similar associations between genotype and PD symptoms.

“This is how we can start thinking about precision medicine in action,” Dr. Alice S. Chen-Plotkin, MD, an assistant professor of neurology and the study’s senior author, said in a news release. “We found that a relatively common genetic variation can both serve as a biomarker for and influence the disease course of Parkinson’s patients. This opens up the possibility of achieving a hallmark of precision medicine: targeted therapies for different ‘versions’ of what was once thought to be a single disease.”