Department of Neurology, MIND Institute, University of California at Davis, Sacramento, CA 95817, USA.
Pharmacogenomics J. 2009 Dec;9(6):411-8. doi: 10.1038/tpj.2009.22. Epub 2009 Jun 2.
Though Deflazacort and prednisone improve clinical endpoints in Duchenne muscular dystrophy (DMD) patients, Deflazacort produces fewer side effects. As mechanisms of improvement and side effect differences remain unknown, we evaluated effects of corticosteroid administration on gene expression in blood of DMD patients. Whole blood was obtained from 14 children and adolescents with DMD treated with corticosteroids (DMD-STEROID) and 20 DMD children and adolescents naïve to corticosteroids (DMD). The DMD-STEROID group was further subdivided into Deflazacort and prednisone groups. Affymetrix U133 Plus 2.0 expression microarrays were used to evaluate mRNA expression. Expression of 524 probes changed with corticosteroids, including genes in iron trafficking and the chondroitin sulfate biosynthesis pathway. Deflazacort compared with prednisone yielded 508 regulated probes, including many involved in adipose metabolism. These genes and pathways help explain mechanisms of efficacy and side effects of corticosteroids, and could provide new treatment targets for DMD and other neuromuscular disorders.
虽然地夫可特和泼尼松可改善杜氏肌营养不良症（DMD）患者的临床终点，但地夫可特的副作用更少。由于改善机制和副作用差异仍不清楚，我们评估了皮质类固醇给药对 DMD 患者血液中基因表达的影响。从接受皮质类固醇治疗的 14 名 DMD 儿童和青少年（DMD-STEROID）和 20 名对皮质类固醇无经验的 DMD 儿童和青少年（DMD）中获得全血。DMD-STEROID 组进一步分为地夫可特和泼尼松组。使用 Affymetrix U133 Plus 2.0 表达微阵列评估 mRNA 表达。皮质类固醇治疗后，524 个探针的表达发生变化，包括铁转运和硫酸软骨素生物合成途径中的基因。与泼尼松相比，地夫可特产生了 508 个调节探针，包括许多与脂肪代谢有关的基因。这些基因和途径有助于解释皮质类固醇的疗效和副作用机制，并可为 DMD 和其他神经肌肉疾病提供新的治疗靶点。
