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α-Synuclein Genetic Variants Predict Faster Motor Symptom Progression in Idiopathic Parkinson Disease

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  • Beate Ritz
  • Shannon L Rhodes
  • Yvette Bordelon
  • Jeff Bronstein

Abstract

Currently, there are no reported genetic predictors of motor symptom progression in Parkinson’s disease (PD). In familial PD, disease severity is associated with higher α-synuclein (SNCA) expression levels, and in postmortem studies expression varies with SNCA genetic variants. Furthermore, SNCA is a well-known risk factor for PD occurrence. We recruited Parkinson’s patients from the communities of three central California counties to investigate the influence of SNCA genetic variants on motor symptom progression in idiopathic PD. We repeatedly assessed this cohort of patients over an average of 5.1 years for motor symptom changes employing the Unified Parkinson’s Disease Rating Scale (UPDRS). Of 363 population-based incident PD cases diagnosed less than 3 years from baseline assessment, 242 cases were successfully re-contacted and 233 were re-examined at least once. Of subjects lost to follow-up, 69% were due to death. Adjusting for covariates, risk of faster decline of motor function as measured by annual increase in motor UPDRS exam score was increased 4-fold in carriers of the REP1 263bp promoter variant (OR 4.03, 95%CI:1.57–10.4). Our data also suggest a contribution to increased risk by the G-allele for rs356165 (OR 1.66; 95%CI:0.96–2.88), and we observed a strong trend across categories when both genetic variants were considered (p for trend = 0.002). Our population-based study has demonstrated that SNCA variants are strong predictors of faster motor decline in idiopathic PD. SNCA may be a promising target for therapies and may help identify patients who will benefit most from early interventions. This is the first study to link SNCA to motor symptom decline in a longitudinal progression study.

Suggested Citation

  • Beate Ritz & Shannon L Rhodes & Yvette Bordelon & Jeff Bronstein, 2012. "α-Synuclein Genetic Variants Predict Faster Motor Symptom Progression in Idiopathic Parkinson Disease," PLOS ONE, Public Library of Science, vol. 7(5), pages 1-8, May.
    • Handle: RePEc:plo:pone00:0036199
    DOI: 10.1371/journal.pone.0036199
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    References listed on IDEAS

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    1. Chuong B Do & Joyce Y Tung & Elizabeth Dorfman & Amy K Kiefer & Emily M Drabant & Uta Francke & Joanna L Mountain & Samuel M Goldman & Caroline M Tanner & J William Langston & Anne Wojcicki & Nicholas, 2011. "Web-Based Genome-Wide Association Study Identifies Two Novel Loci and a Substantial Genetic Component for Parkinson's Disease," PLOS Genetics, Public Library of Science, vol. 7(6), pages 1-14, June.
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    Cited by:

    1. Xiao-Ying Wang & Wen-Yan Kang & Qiong Yang & Lin-Yuan Zhang & Sheng-Di Chen & Jun Liu, 2014. "Using Gastrocnemius sEMG and Plasma α-Synuclein for the Prediction of Freezing of Gait in Parkinson's Disease Patients," PLOS ONE, Public Library of Science, vol. 9(2), pages 1-5, February.
    2. James R Roede & Karan Uppal & Youngja Park & Kichun Lee & Vilinh Tran & Douglas Walker & Frederick H Strobel & Shannon L Rhodes & Beate Ritz & Dean P Jones, 2013. "Serum Metabolomics of Slow vs. Rapid Motor Progression Parkinson’s Disease: a Pilot Study," PLOS ONE, Public Library of Science, vol. 8(10), pages 1-1, October.

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