Objectives: The ubiquitin/proteasome system is one of the main axes of the pathogenesis of Parkinson's disease (PD). Small ubiquitin-related modifier (SUMO) proteins are involved in many biochemical events including regulation of transcriptional activity, modulation of signal transduction pathways, and response to cellular stress indicating a role for SUMO in the ubiquitin/proteasome system.Methods: In this study, our aim was to examine the prevalence of SUMO gene variants and their clinical associations in PD. Fifty-four consecutively recruited PD patients (34 male, 20 female) and 74 age-gender matched healthy controls (37 male, 37 female) were included. SUMO1, 2, 3 and 4 genes were screened by a next generation sequencing method using blood samples of participants. Single nucleotide polymorphisms (SNPs) with a significantly altered prevalence were determined by Bonferroni correction.Results: Two SNPs in the SUMO4 gene (rs237025 and rs237024) and two SNPs in the SUMO3 gene (rs180313 and rs235293) were found to have altered prevalence in PD. Although there was no association among these SNPs and clinical features of the patients, an increased family history of cancer was found in patients with SUMO3 gene variants.Discussion: Several SUMO SNPs were identified for the first time in PD patients suggesting that SUMO is involved in the pathophysiology of the disease. rs237025 has also been associated with diabetes mellitus indicating a pathogenic mechanism for SUMO that is shared with other degenerative disorders.

中文翻译：

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帕金森氏病中小泛素相关修饰物（SUMO）3和SUMO4基因多态性。

目的：泛素/蛋白酶体系统是帕金森氏病（PD）发病机理的主轴之一。小泛素相关修饰因子（SUMO）蛋白参与许多生化事件，包括转录活性的调节，信号转导途径的调节以及对细胞应激的反应，表明SUMO在泛素/蛋白酶体系统中的作用。我们的目的是检查SUMO基因变异的发生率及其在PD中的临床关联。包括五十四名连续招募的PD患者（男34例，女20例）和74名按性别分类的健康对照者（男37例，女37例）。使用参与者的血液样本，通过下一代测序方法筛选了SUMO1、2、3和4基因。通过Bonferroni校正确定了患病率显着改变的单核苷酸多态性（SNP）。结果：发现SUMO4基因中的两个SNP（rs237025和rs237024）和SUMO3基因中的两个SNP（rs180313和rs235293）的PD患病率发生了改变。尽管这些SNP与患者的临床特征之间没有关联，但是在SUMO3基因变异的患者中发现了家族史增加的癌症。讨论：PD患者首次发现了几种SUMO SNP，表明SUMO参与了该疾病的病理生理学。rs237025也与糖尿病相关，表明SUMO的致病机制与其他退行性疾病共有。发现SUMO4基因中的两个SNP（rs237025和rs237024）和SUMO3基因中的两个SNP（rs180313和rs235293）已经改变了PD的患病率。尽管这些SNP与患者的临床特征之间没有关联，但是在SUMO3基因变异的患者中发现了家族史增加的癌症。讨论：PD患者首次发现了几种SUMO SNP，表明SUMO参与了该疾病的病理生理学。rs237025也与糖尿病相关，表明SUMO的致病机制与其他退行性疾病共有。发现SUMO4基因中的两个SNP（rs237025和rs237024）和SUMO3基因中的两个SNP（rs180313和rs235293）改变了PD的患病率。尽管这些SNP与患者的临床特征之间没有关联，但是在SUMO3基因变异的患者中发现了家族史增加的癌症。讨论：PD患者首次发现了几种SUMO SNP，表明SUMO参与了该疾病的病理生理学。rs237025也与糖尿病相关，表明SUMO的致病机制与其他退行性疾病共有。讨论：SUMO3基因变异的患者中发现了家族癌症的增加。讨论：在PD患者中首次鉴定出几种SUMO SNP，表明SUMO参与了该疾病的病理生理。rs237025也与糖尿病相关，表明SUMO的致病机制与其他退行性疾病共有。讨论：SUMO3基因变异的患者中发现了家族癌症的增加。讨论：在PD患者中首次鉴定出几种SUMO SNP，表明SUMO参与了该疾病的病理生理。rs237025也与糖尿病相关，表明SUMO的致病机制与其他退行性疾病共有。