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Corticosteroid effects on blood gene expression in Duchenne muscular dystrophy

The Pharmacogenomics Journal volume 9, pages 411–418 (2009)Cite this article

Abstract

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.

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Acknowledgements

We thank the nurses and study coordinators who helped with these studies at Cincinnati Children's Hospital Medical Center. We also thank the Affymetrix cores for processing the samples. This study was supported by NIH/NINDS Grants (NS043252 and NS056302, FRS), support from Cincinnati Children's Hospital Medical Center (BW), and support from the M.I.N.D. Institute at the University of California at Davis (FRS, LL, IL, WW, MA).

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Authors and Affiliations

  1. Department of Neurology, MIND Institute, University of California at Davis, Sacramento, CA, USA

    L Lit, F R Sharp, M Apperson, D Z Liu, W L Walker, I Liao, H Xu & B P Ander

  2. Department of Pediatric Neurology, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, OH, USA

    B Wong

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  1. L Lit
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Correspondence to L Lit.

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Supplementary Information accompanies the paper on the The Pharmacogenomics Journal website (http://www.nature.com/tpj)

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Lit, L., Sharp, F., Apperson, M. et al. Corticosteroid effects on blood gene expression in Duchenne muscular dystrophy. Pharmacogenomics J 9, 411–418 (2009). https://doi.org/10.1038/tpj.2009.22

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