There is great heterogeneity in both the clinical presentation and rate of disease progression among patients with Parkinson’s disease (PD). This can pose prognostic difficulties in a clinical setting, and a greater understanding of the risk factors that contribute to modify disease course is of clear importance for optimizing patient care and clinical trial design. Genetic variants in SNCA are an established risk factor for PD and are candidates to modify disease presentation and progression. This systematic review aimed to summarize all available primary research reporting the association of SNCA polymorphisms with features of PD. We systematically searched PubMed and Web of Science, from inception to 1 June 2020, for studies evaluating the association of common SNCA variants with age at onset (AAO) or any clinical feature attributed to PD in patients with idiopathic PD. Fifty-eight studies were included in the review that investigated the association between SNCA polymorphisms and a broad range of outcomes, including motor and cognitive impairment, sleep disorders, mental health, hyposmia, or AAO. The most reproducible findings were with the REP1 polymorphism or rs356219 and an earlier AAO, but no clear associations were identified with an SNCA polymorphism and any individual clinical outcome. The results of this comprehensive summary suggest that, while there is evidence that genetic variance in the SNCA region may have a small impact on clinical outcomes in PD, the mechanisms underlying the association of SNCA polymorphisms with PD risk may not be a major factor driving clinical heterogeneity in PD.

帕金森病 (PD) 患者的临床表现和疾病进展速度都存在很大的异质性。这可能会给临床环境中的预后带来困难，而更好地了解有助于改变病程的风险因素对于优化患者护理和临床试验设计具有明显的重要性。SNCA中的遗传变异是 PD 的既定危险因素，并且是改变疾病表现和进展的候选者。本系统综述旨在总结所有可用的主要研究报告SNCA多态性与 PD 特征的关联。我们系统地搜索了 PubMed 和 Web of Science，从开始到 2020 年 6 月 1 日，以获取评估常见SNCA关联的研究特发性 PD 患者的发病年龄 (AAO) 或归因于 PD 的任何临床特征的变异。该评价纳入了 58 项研究，这些研究调查了SNCA多态性与广泛结果之间的关联，包括运动和认知障碍、睡眠障碍、心理健康、嗅觉减退或 AAO。最可重复的发现是 REP1 多态性或 rs356219 和早期的 AAO，但没有发现与SNCA多态性和任何个体临床结果的明确关联。该综合总结的结果表明，虽然有证据表明SNCA区域的遗传变异可能对 PD 的临床结果产生很小的影响，但具有 PD 风险的SNCA多态性可能不是驱动 PD 临床异质性的主要因素。