Mohammadi Raziyeh, Shirazi Mahdi, Sadat-Madani Sayedeh Fatemeh, Yeo Cheng Long Matthew Zachary, Singh Corrine Lee, Tan Jayne Y, Deng Xiao, Hashemi Fard Seyed Majid, Ng Samuel Y E, Ng Adeline S L, Tan Louis C S, Saffari Seyed Ehsan
Duke-NUS Medical School, National University of Singapore, Singapore 169857, Singapore.
Department of Physics, Isfahan University of Technology, Isfahan 84156-83111, Iran.
Int J Mol Sci. 2025 Jun 23;26(13):6001. doi: 10.3390/ijms26136001.
The gene, encoding alpha-synuclein, is implicated in the pathogenesis of Parkinson's disease (PD), with several single-nucleotide polymorphisms (SNPs) linked to increased risk. This study systematically evaluated the association between common polymorphisms and PD through a meta-analysis of cohort and case-control studies published before 20 November 2023. Eligible studies were identified via comprehensive searches of PubMed, Scopus, and Web of Science, and pooled odds ratios with 95% confidence intervals were calculated under allelic, dominant, and recessive models. Heterogeneity and publication bias were assessed, and subgroup and sensitivity analyses were performed. Twenty-seven studies were included. SNP showed consistent associations with PD across all models, with low heterogeneity and no evidence of publication bias. rs356219 and rs356165 were also significantly associated with PD, although regional differences contributed to heterogeneity. In contrast, rs2583988 showed marginal significance in the allelic model, which was lost after sensitivity analyses. No associations were found under dominant or recessive models for this SNP. These findings confirm rs11931074 as a robust PD risk variant and support the roles of rs356219 and rs356165 while suggesting weaker evidence for rs2583988. Large, multi-ethnic studies are warranted to elucidate underlying mechanisms and support precision medicine in PD.
编码α-突触核蛋白的基因与帕金森病（PD）的发病机制有关，有几种单核苷酸多态性（SNP）与患病风险增加相关。本研究通过对2023年11月20日前发表的队列研究和病例对照研究进行荟萃分析，系统评估了常见多态性与PD之间的关联。通过全面检索PubMed、Scopus和Web of Science确定符合条件的研究，并在等位基因、显性和隐性模型下计算合并优势比及95%置信区间。评估了异质性和发表偏倚，并进行了亚组分析和敏感性分析。纳入了27项研究。SNP在所有模型中均显示出与PD的一致关联，异质性低且无发表偏倚的证据。rs356219和rs356165也与PD显著相关，尽管区域差异导致了异质性。相比之下，rs2583988在等位基因模型中显示出边缘显著性，但在敏感性分析后消失。该SNP在显性或隐性模型下未发现关联。这些发现证实rs11931074是一个可靠的PD风险变异体，支持rs356219和rs356165的作用，同时表明rs2583988的证据较弱。需要开展大规模的多民族研究来阐明潜在机制并支持PD的精准医学。
