Variants in the SNCA Locus Are Associated With the Progression of Parkinson's Disease
Variants in the SNCA Locus Are Associated With the Progression of Parkinson's Disease
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SNCA 基因座的变异与帕金森病的进展相关
DOI：
10.3389/fnagi.2019.00110
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发表时间：
2019-05-21
影响因子：
4.8
通讯作者：
Liu, Jun
中科院分区：
文献类型：
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作者：
Luo, Ningdi;Li, Yuanyuan;Liu, Jun
背景资料：遗传因素对帕金森病（PD）易感性有众所周知的影响;然而，以前没有研究使用前瞻性随访研究调查SNCA突变对PD自然史的影响。本研究的目的是评估SNCA变异对PD患者预后症状的危险因素。方法：50例PD患者和38例经v-PSG证实的PD+RBD患者，中位随访时间为30个月。所有患者均在基线和随访时进行综合临床评估，并分析SNCA的6个SNP（rs356165，rs3857053，rs 1045722，rs 894278，rs356186和rs356219）。采用考克斯比例风险回归模型和Kaplan-Meier曲线分析评估SNCA变异与主要和次要进展结局之间的相关性。结果：根据临床评估，我们发现嗅觉减退更容易恶化。回归分析显示，具有rs 1045722的T等位基因和rs356219的G等位基因的患者进展到H-Y阶段的风险分别降低34%和20%（p = 0.022; p = 0.005）。而对于rs 894278，G等位基因患者显示嗅觉功能障碍的风险降低47%（p = 0.029）。进一步的亚组分析显示，具有rs356219/G的PD+RBD患者在H-Y分期和莫卡评分上表现出30%和20%的进展风险降低（p = 0.038; p = 0.045）。结论：我们的研究结果表明，SNCA的遗传变异可能有助于PD的变异性自然进展，并可能被用作一个预后指标。
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.