Variations in the length of the alpha-synuclein gene promoter's dinucleotide repeat sequence have been linked to Parkinson's disease in a study analyzing DNA samples from more than 5,300 subjects around the world.
Mutations in the alpha-synuclein (SNCA) gene have been implicated before in Parkinson's disease (PD), but only within certain families and rarely among the general population.
“Our study demonstrates that the SNCA gene is not only a rare cause of autosomal dominant Parkinson disease in some families, but also a susceptibility gene for PD at the population level,” reported Dr. Demetrius M. Maraganore of the Mayo Clinic, Rochester, Minn., and his associates.
“Based on our results, we estimate that REP1 [the alpha-synuclein gene promoter's dinucleotide repeat sequence] locus variability may explain approximately 3% of the risk in the general population,” the researchers said (JAMA 2006;296:661–70).
They used data from the Genetic Epidemiology of Parkinson's Disease Consortium to investigate SNCA gene mutations in what they described as “the largest case-control study of PD to date.” The consortium collects and shares biospecimens and data collected at multiple sites worldwide.
For this study, DNA analysis was done on samples from 2,692 patients with PD and 2,652 unrelated control subjects.
Variability in the length of a dinucleotide repeat sequence within the SNCA promoter was found to be associated with PD susceptibility.
If further study finds that this risk is conferred via a mechanism of gene overexpression, interventions targeting SNCA expression may reduce the risk of developing PD in susceptible populations. It remains uncertain, however, whether therapies to reduce SNCA expression would affect the progression of existing PD, Dr. Maraganore and his associates noted.