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Alpha-synuclein repeat variants and survival in Parkinson's disease

Authors


  • Funding agencies: The Goldwurm site acknowledges the funding support of the Italian Telethon Foundation (grant no.: GTB07001) and the “Fondazione Grigioni per il Morbo di Parkinson.” The Maraganore site acknowledges the funding support of the National Institutes of Health (R01 ES10751). The Morrison site acknowledges the funding support of the Medical Research Council UK, Midlands Neuroscience Teaching and Research Fund, and Queen Elizabeth Hospital Birmingham Charity. The Theuns/Van Broeckhoven site acknowledges the funding support of the Interuniversity Attraction Poles program of the Belgian Science Policy Office, the Foundation for Alzheimer Research, the Belgian Parkinson Foundation, the Methusalem Excellence Program of the Flemish Government, the Research Foundation Flanders, the Agency for Innovation by Science and Technology Flanders, and the Special Research Fund of the University of Antwerp, Antwerp, Belgium. The Wszolek site acknowledges the funding support of the National Institutes of Health (P50 NS072187) and the Mayo Clinic Florida Research Committee CR program.

  • Relevant conflicts of interest/financial disclosures: Demetrius M. Maraganore, MD has licensed an invention to Alnylam Pharmaceuticals, Inc. regarding a method to treat Parkinson's disease. He has received less than $25,000 in royalties. The remaining authors have nothing to declare.

ABSTRACT

Objectives

To determine whether α-synuclein dinucleotide repeat (REP1) genotypes are associated with survival in Parkinson's disease (PD).

Methods

Investigators from the Genetic Epidemiology of Parkinson's Disease Consortium provided REP1 genotypes and baseline and follow-up clinical data for cases. The primary outcome was time to death. Cox proportional hazards regression models were used to assess the association of REP1 genotypes with survival.

Results

Twenty-one sites contributed data for 6,154 cases. There was no significant association between α-synuclein REP1 genotypes and survival in PD. However, there was a significant association between REP1 genotypes and age at onset of PD (hazard ratio: 1.06; 95% confidence interval: 1.01-1.10; P value = 0.01).

Conclusions

In our large consortium study, α-synuclein REP1 genotypes were not associated with survival in PD. Further studies of α-synuclein's role in disease progression and long-term outcomes are needed. © 2014 International Parkinson and Movement Disorder Society

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