AUTHOR=Luo Ningdi , Li Yuanyuan , Niu Mengyue , Zhou Liche , Yao Mengsha , Zhu Lin , Ye Guanyu , Kang Wenyan , Liu Jun 

TITLE=Variants in the SNCA Locus Are Associated With the Progression of Parkinson's Disease

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=11

YEAR=2019

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2019.00110

DOI=10.3389/fnagi.2019.00110

ISSN=1663-4365

ABSTRACT=<p><bold>Background:</bold> Genetic factors have a well-known influence on Parkinson's disease (PD) susceptibility; however, no previous studies have investigated the influence of <italic>SNCA</italic> mutations on the natural history of PD using a prospective follow-up study. The aim of this study was to assess the risk factors of variation of <italic>SNCA</italic> on the prognosis symptoms of PD patients.</p><p><bold>Methods:</bold> Fifty PD patients were recruited with 38 v-PSG confirmed PD+RBD patients, and the median follow-up period was 30 months. All patients underwent a comprehensive clinical evaluation at baseline and follow-up, and six SNPs of <italic>SNCA</italic> (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 <italic>SNCA</italic> variation and the primary and secondary progression outcomes.</p><p><bold>Results:</bold> Based on the clinical assessment, we found that hyposmia was substantially easier to aggravate. Regression analysis showed that patients with the T allele of rs1045722 and the G allele of rs356219 presented a 34 and 20% decreased risk of progression to the H-Y stage, respectively (<italic>p</italic> = 0.022; <italic>p</italic> = 0.005). While for rs894278, G allele patients showed a 47% decreased risk of olfactory dysfunction (<italic>p</italic> = 0.029). 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 (<italic>p</italic> = 0.038; <italic>p</italic> = 0.045).</p><p><bold>Conclusions:</bold> Our results indicated that genetic variation in <italic>SNCA</italic> may contribute to variability natural progression of PD and could possibly be used as a prognostic marker.</p>