Variants In The SNCA Locus Are Associated With The Progression Of Parkinson's Disease

Objective Genetic factors have a well-known influence on Parkinson disease(PD)susceptibility,in which SNCA is one of the most prominent hallmarks,however,no previous studies have investigated the influence of SNCA mutations on the natural history of Parkinson's disease using prospective follow-up study.The aim of this study was to assess the risk factors of variation of SNCA on the prognosis symptoms in patients with PD.Methods Fifty PD patients were recruited were recruited from Department of Neurology,Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine,and the median follow-up period was 30 months,while 38 PD-RBD patients were enrolled with PSG confirmed.All patients underwent a comprehensive clinical evaluation at baseline and follow-up,six SNPs of SNCA(rs356165,rs3857053,rs1045722,rs894278,rs356186,and rs356219)were analyzed.Cox proportional hazards regression models and Kaplan-Meier plot analysis were used to assess the associations between the SNCA variation and the primary and secondary progression outcomes.Results 1.Based on the clinical assessment,PD patients showed varying degrees of progress in both motor and non-motor symptoms.We found higher H-Y stage,UPDRS ? and ? scores and NMSQ(p?0.001),worsen constipation and olfactory function(p=0.003;p=0.022),and more LEDD(p<0.001)after the 30-month period,in which PD patients with RBD was substantially easier to aggravate in UPDRS ?,NMSQ and SCOPA-AUT(p=0.007;p<0.001;p<0.001).2.Regression analysis showed that patients with T allele of rs1045722 and G allele of rs356219 presented a 34% and 20% decreased risk of progression to the H-Y stage respectively(p=0.022;p=0.005).While for rs894278,G allele-patients showed a 47% decreased risk of olfactory dysfunction(p=0.029).3.Further subgroup analysis showed that PD+RBD patients with rs356219/G exhibited a 30% and 20% decreased risk of progression on the H-Y stage and MOCA score(p=0.038;p=0.045).Conclusions Our results indicated that genetic variation in SNCA may contribute to variability natural progression of PD and could possibly be used as a prognostic marker.