Tian L J, Cao J H, Deng X Q, Zhang C L, Qian T, Song X X, Huang B S
Clinical Laboratory, Children's Hospital, Xuzhou, Jiangsu Province, China
Clinical Laboratory, Children's Hospital, Xuzhou, Jiangsu Province, China.
Genet Mol Res. 2014 Feb 28;13(1):1402-11. doi: 10.4238/2014.February.28.13.
Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy with no cure currently available. In this study, using two microarray data sets obtained from the Gene Expression Omnibus database, we conducted a dysfunctional pathway-enrichment analysis and investigated deregulated genes that are specific to different phases of the disease in order to determine pathogenic characteristics in the progression of DMD. We identified 41 and 33 dysfunctional pathways that were enriched with differentially expressed genes in presymptomatic patients and in symptomatic patients, respectively. Over 70% of pathways were shared between both phases and many of them involved the inflammatory process, suggesting that inflammatory cascades were induced soon after the birth of the patients. Further investigation showed that presymptomatic patients performed better with respect to muscle regeneration and cardiac muscle calcium homeostasis maintenance. Neuronal nitric oxide synthase, dihydropyridine receptors, sarcoplasmic/endoplasmic reticulum calcium ATPase, and phospholamban may serve as potential targets for further molecular diagnostic tests. Our results may provide a better understanding for the treatment of DMD.
杜氏肌营养不良症（DMD）是最常见的肌营养不良症形式，目前尚无治愈方法。在本研究中，我们使用从基因表达综合数据库获得的两个微阵列数据集，进行了功能失调通路富集分析，并研究了疾病不同阶段特有的失调基因，以确定DMD进展过程中的致病特征。我们分别在症状前患者和症状患者中鉴定出41条和33条富含差异表达基因的功能失调通路。超过70%的通路在两个阶段之间是共享的，其中许多通路涉及炎症过程，这表明患者出生后不久就会引发炎症级联反应。进一步研究表明，症状前患者在肌肉再生和心肌钙稳态维持方面表现更好。神经元型一氧化氮合酶、二氢吡啶受体、肌浆网/内质网钙ATP酶和受磷蛋白可能作为进一步分子诊断测试的潜在靶点。我们的结果可能为DMD的治疗提供更好的理解。
