Salivary microR-153 and microR-223 Levels as Potential Diagnostic Biomarkers of Idiopathic Parkinson's Disease
Salivary microR-153 and microR-223 Levels as Potential Diagnostic Biomarkers of Idiopathic Parkinson's Disease
复制标题
DOI：
10.1002/mds.27935
复制
发表时间：
2019-12-04
影响因子：
8.6
通讯作者：
Schipper, Hyman M.
中科院分区：
文献类型：
--
作者：
Cressatti, Marisa;Juwara, Lamin;Schipper, Hyman M.
帕金森病（PD）是成人中最常见的运动障碍，影响世界65岁以上人口的2%。目前不存在临床环境中常规使用的诊断生物标志物。microRNA（miRNAs）的失调与包括PD在内的各种神经退行性疾病有关。不同的miRNA已被证明参与α-突触核蛋白的调节，这是PD发病机制中的关键因素; miR-153和miR-223在帕金森病GFAP.HMOX1转基因小鼠的脑和血清中下调，其中它们直接调节α-突触核蛋白。目的探讨唾液中miR-153和miR-223是否在原发性PD中同样下调，并可作为诊断PD的生物标志物。方法采用逆转录酶定量聚合酶链反应检测77名非神经系统对照和83名PD患者唾液中miR-153和miR-223的水平。血红素氧合酶-1和α-突触核蛋白的水平采用酶联免疫吸附测定法进行测量。根据年龄、性别、药物暴露、疾病持续时间和相关合并症调整分析。结果与非神经系统对照组相比，PD患者唾液中miR-153和miR-223的对数转换表达水平显著降低。miRNA表达水平不随疾病进展而变化（Hoehn和Yahr分期）。对于miR-153和miR-223，区分对照和PD患者的受试者工作特征曲线下面积分别为79%（95%置信区间，61%-96%）和77%（95%置信区间，59%-95%）。miRNA与寡聚体α-突触核蛋白、总α-突触核蛋白或血红素加氧酶-1蛋白的比率没有提高测试的准确性。结论唾液中miR-153和miR-223水平可作为诊断原发性PD的有效、无创和相对廉价的生物标志物。(c)2019国际帕金森和运动障碍协会
Background Parkinson's disease (PD) is the most common movement disorder among adults, affecting 2% of the world population older than 65 years of age. No diagnostic biomarker for routine use in clinical settings currently exists. Dysregulation of microRNAs (miRNAs) has been implicated in various neurodegenerative conditions, including PD. Distinct miRNAs have been demonstrated to be involved in the regulation of alpha-synuclein, a key player in PD pathogenesis; miR-153 and miR-223 are downregulated in the brain and serum of parkinsonian GFAP.HMOX1 transgenic mice where they directly regulate alpha-synuclein. Objective To ascertain whether salivary miR-153 and miR-223 are similarly downmodulated in, and may serve as diagnostic biomarkers of, idiopathic PD. Methods Using reverse transcriptase quantitative polymerase chain reaction, miR-153 and miR-223 levels were evaluated in the saliva of 77 non-neurological controls and 83 PD patients. Levels of heme oxygenase-1 and alpha-synuclein were measured using enzyme-linked immunosorbent assay. Analyses were adjusted by age, sex, medication exposure, disease duration, and relevant comorbidities. Results Log-transformed expression levels of miR-153 and miR-223 were significantly decreased in the saliva of human PD patients in comparison with nonneurological controls. The miRNA expression levels did not change as a function of disease progression (Hoehn and Yahr staging). The area under the receiver operating characteristic curve separating controls from PD patients was 79% (95% confidence interval, 61%-96%) for miR-153 and 77% (95% confidence interval, 59%-95%) for miR-223. The ratios of miRNAs to oligomeric alpha-synuclein, total alpha-synuclein, or heme oxygenase-1 protein did not improve accuracy of the test. Conclusion Salivary miR-153 and miR-223 levels may serve as useful, noninvasive, and relatively inexpensive diagnostic biomarkers of idiopathic PD. (c) 2019 International Parkinson and Movement Disorder Society