PLoS One. 2012;7(5):e36199. Epub 2012 May 15.
Ritz B, Rhodes SL, Bordelon Y, Bronstein J.
Source
Department of Epidemiology, University of California Los Angeles, Los Angeles, California, United States of America.
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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