一项研究发现，与糖尿病有关的两个基因在帕金森病（PD）病人身上出现了表达改变，而且可能充当帕金森病（PD）早期诊断与进程监测的可能的生物标记。

几项研究已经鉴别出帕金森病（PD）病人血液中的分子特征有别于健康人。为了研究这种疾病可能的生物标记物，Jose A. Santiago 和Judith A. Potashkin荟萃分析了46名健康人与83名帕金森病（PD）病人的基因表达模式的4项微阵列比较研究。作者从这两个对比组识别出2个表达差异最显著的基因，一个是肝细胞核因子4α（HNF4A），另一个是多聚嘧啶序列结合蛋白1（PTBP1），此前发现它们都与糖尿病有联系。

对来自两个独立的临床研究的101名帕金森病（PD）病人以及对照组的91名健康人的血样的进一步分析证实了HNF4A 和PTBP1基因在这两个组里的表达有差异。与对照组健康人相比，帕金森病（PD）病人的HNF4A mRNA的丰富程度更高，而且与疾病严重性有相关性；而与对照组健康人相比，帕金森病（PD）病人的PTBP1 mRNA较低。

帕金森病（PD）病人的这两种基因的表达在3年时间里都发生了显著变化，这提示它们有潜力充当监测这种疾病的临床进程的生物标记物。对这些基因作为生物标记物的有效性的一项测试显示，帕金森病（PD）准确诊断率为90%。作者说，这两种基因的mRNA水平可能有助于诊断早期帕金森病病人，并且追踪该病的进程。（来源：生物360）

Network-based metaanalysis identifies HNF4A and PTBP1 as longitudinally dynamic biomarkers for Parkinson’s disease

Abstract  Environmental and genetic factors are likely to be involved in the pathogenesis of Parkinson’s disease (PD), the second most prevalent neurodegenerative disease among the elderly. Network-based metaanalysis of four independent microarray studies identified the hepatocyte nuclear factor 4 alpha (HNF4A), a transcription factor associated with gluconeogenesis and diabetes, as a central regulatory hub gene up-regulated in blood of PD patients. In parallel, the polypyrimidine tract binding protein 1 (PTBP1), involved in the stabilization and mRNA translation of insulin, was identified as the most down-regulated gene. Quantitative PCR assays revealed that HNF4A and PTBP1 mRNAs were up- and down-regulated, respectively, in blood of 51 PD patients and 45 controls nested in the Diagnostic and Prognostic Biomarkers for Parkinson’s Disease. These results were confirmed in blood of 50 PD patients compared with 46 healthy controls nested in the Harvard Biomarker Study. Relative abundance of HNF4A mRNA correlated with the Hoehn and Yahr stage at baseline, suggesting its clinical utility to monitor disease severity. Using both markers, PD patients were classified with 90% sensitivity and 80% specificity. Longitudinal performance analysis demonstrated that relative abundance of HNF4A and PTBP1 mRNAs significantly decreased and increased, respectively, in PD patients during the 3-y follow-up period. The inverse regulation of HNF4A and PTBP1 provides a molecular rationale for the altered insulin signaling observed in PD patients. The longitudinally dynamic biomarkers identified in this study may be useful for monitoring disease-modifying therapies for PD.

原文链接：http://www.pnas.org/content/early/2015/01/27/1423573112.full.pdf+html