Corticosteroid effects on blood gene expression in Duchenne muscular dystrophy.
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.
Lit
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Department of Neurology, MIND Institute, University of California at Davis, Sacramento, CA 95817, USA. llit@ucdavis.edu
Sharp
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Apperson
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Liu
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Walker
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Liao
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Xu
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Ander
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Wong
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B
D000273:Adipose Tissue / Q000378:metabolism; D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002809:Chondroitin Sulfates / Q000096:biosynthesis; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D006801:Humans; D007501:Iron / Q000378:metabolism; D020388:Muscular Dystrophy, Duchenne / Q000097:blood* / Q000188:drug therapy / Q000235:genetics*; D011241:Prednisone / Q000627:therapeutic use*; D011282:Pregnenediones / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000097:blood; D012189:Retrospective Studies
D011282:Pregnenediones; D012333:RNA, Messenger; D002809:Chondroitin Sulfates; D007501:Iron; C021988:deflazacort; D011241:Prednisone