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. 2012;7(5):e36199.
doi: 10.1371/journal.pone.0036199. Epub 2012 May 15.

α-Synuclein genetic variants predict faster motor symptom progression in idiopathic Parkinson disease

Beate Ritz  1 , Shannon L Rhodes, Yvette Bordelon, Jeff Bronstein
Affiliations

α-Synuclein genetic variants predict faster motor symptom progression in idiopathic Parkinson disease

Beate Ritz et al. PLoS One. 2012.

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

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References

    1. Global PD Survey Steering Committee. Factors impacting on quality of life in Parkinson’s disease: results from an international survey. Mov Disord. 2002;17:60–67. - PubMed
    1. Poewe W. The need for neuroprotective therapies in Parkinson’s disease: a clinical perspective. Neurology. 2006;66:S2–9. - PubMed
    1. Louis ED, Tang MX, Cote L, Alfaro B, Mejia H, et al. Progression of parkinsonian signs in Parkinson disease. Arch Neurol. 1999;56:334–337. - PubMed
    1. Jankovic J, Kapadia AS. Functional decline in Parkinson disease. Arch Neurology. 2001;58:1611–1615. - PubMed
    1. Alves G, Wentzel-Larsen T, Aarsland D, Larsen JP. Progression of motor impairment and disability in Parkinson disease: a population-based study. Neurology. 2005;65:1436–1441. - PubMed

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