Journal
FRONTIERS IN AGING NEUROSCIENCE
Volume 11, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fnagi.2019.00110
Keywords
Parkinson's disease; RBD; SNCA; SNP; disease progression
Categories
Funding
- National Key Research and Development Program [2016YFC1306505]
- National Natural Science Foundation of China [81501097, 81873778]
- Shanghai Municipal Education Commission-Basic Key Project [18JC1420300]
- Shanghai Clinical Collaboration Construction Project of Chinese and Western Medicine [ZY20182020-FWTX-1104]
- Shanghai Sailing Program [19YF1429800]
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Background: Genetic factors have a well-known influence on Parkinson's disease (PD) susceptibility; however, no previous studies have investigated the influence of SNCA 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 SNCA on the prognosis symptoms of PD patients. Methods: 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 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: 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 (p = 0.022; p = 0.005). While for rs894278, G allele patients showed a 47% decreased risk of olfactory dysfunction (p = 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 (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.
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