α-synuclein genetic variants predict faster motor symptom progression in idiopathic parkinson diseaseα-synuclein遗传变异预测更快的汽车特发性帕金森病的症状.pdfVIP

a-Synuclein Genetic Variants Predict Faster Motor Symptom Progression in Idiopathic Parkinson Disease 1,2 1 2 2 Beate Ritz *, Shannon L. Rhodes , Yvette Bordelon , Jeff Bronstein 1 Department of Epidemiology, University of California Los Angeles, Los Angeles, California, United States of America, 2 Department of Neurology, 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 a-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 co