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Published in: neurogenetics 2/2009

01-04-2009 | Original Article

Gene expression in blood of subjects with Duchenne muscular dystrophy

Authors: Brenda Wong, Donald L. Gilbert, Wynn L. Walker, Isaac H. Liao, Lisa Lit, Boryana Stamova, Glen Jickling, Michelle Apperson, Frank R. Sharp

Published in: Neurogenetics | Issue 2/2009

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Abstract

The objective of this study was to examine RNA expression in blood of subjects with Duchenne muscular dystrophy (DMD). Whole blood was collected into PAX gene tubes and RNA was isolated for 3- to 20-year-old males with DMD (n = 34) and for age- and gender-matched normal healthy controls (n = 21). DMD was confirmed by genetic testing in all subjects. RNA expression was measured on Affymetrix whole-genome human U133 Plus 2.0 GeneChips. Using a Benjamini–Hochberg false discovery rate of 0.05 to correct for multiple comparisons, an unpaired t test for DMD versus controls yielded 10,763 regulated probes with no fold change cutoff, 1,467 probes with >|1.5|-fold change, 191 probes with >|2.0|-fold change, and 59 probes with a >|2.5|-fold change. These genes (probes) separated DMD from controls using cluster analyses. Almost all of the genes regulated in peripheral blood were different from the genes reported to be regulated in diseased muscle of subjects with DMD. It is proposed that the genes regulated in blood of subjects with Duchenne muscular dystrophy are indicative, at least in part, of the immune response to the diseased DMD muscle. The regulated genes might be used to monitor therapy or provide novel targets for immune-directed therapy for DMD.
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Literature
3.
go back to reference Moxley RT 3rd, Ashwal S, Pandya S, Connolly A, Florence J, Mathews K, Baumbach L, McDonald C, Sussman M, Wade C (2005) Practice parameter: corticosteroid treatment of Duchenne dystrophy: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology 64:13–20PubMed Moxley RT 3rd, Ashwal S, Pandya S, Connolly A, Florence J, Mathews K, Baumbach L, McDonald C, Sussman M, Wade C (2005) Practice parameter: corticosteroid treatment of Duchenne dystrophy: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology 64:13–20PubMed
4.
go back to reference Griggs RC, Moxley RT 3rd, Mendell JR, Fenichel GM, Brooke MH, Pestronk A, Miller JP, Cwik VA, Pandya S, Robison J et al (1993) Duchenne dystrophy: randomized, controlled trial of prednisone (18 months) and azathioprine (12 months). Neurology 43:520–527PubMed Griggs RC, Moxley RT 3rd, Mendell JR, Fenichel GM, Brooke MH, Pestronk A, Miller JP, Cwik VA, Pandya S, Robison J et al (1993) Duchenne dystrophy: randomized, controlled trial of prednisone (18 months) and azathioprine (12 months). Neurology 43:520–527PubMed
8.
go back to reference Raju R, Dalakas MC (2005) Gene expression profile in the muscles of patients with inflammatory myopathies: effect of therapy with IVIg and biological validation of clinically relevant genes. Brain 128:1887–1896 doi:10.1093/brain/awh518 CrossRefPubMed Raju R, Dalakas MC (2005) Gene expression profile in the muscles of patients with inflammatory myopathies: effect of therapy with IVIg and biological validation of clinically relevant genes. Brain 128:1887–1896 doi:10.​1093/​brain/​awh518 CrossRefPubMed
9.
go back to reference Tang Y, Schapiro MB, Franz DN, Patterson BJ, Hickey FJ, Schorry EK, Hopkin RJ, Wylie M, Narayan T, Glauser TA, Gilbert DL, Hershey AD, Sharp FR (2004) Blood expression profiles for tuberous sclerosis complex 2, neurofibromatosis type 1, and Down’s syndrome. Ann Neurol 56:808–814 doi:10.1002/ana.20291 CrossRefPubMed Tang Y, Schapiro MB, Franz DN, Patterson BJ, Hickey FJ, Schorry EK, Hopkin RJ, Wylie M, Narayan T, Glauser TA, Gilbert DL, Hershey AD, Sharp FR (2004) Blood expression profiles for tuberous sclerosis complex 2, neurofibromatosis type 1, and Down’s syndrome. Ann Neurol 56:808–814 doi:10.​1002/​ana.​20291 CrossRefPubMed
10.
go back to reference Tang Y, Xu H, Du X, Lit L, Walker W, Lu A, Ran R, Gregg JP, Reilly M, Pancioli A, Khoury JC, Sauerbeck LR, Carrozzella JA, Spilker J, Clark J, Wagner KR, Jauch EC, Chang DJ, Verro P, Broderick JP, Sharp FR (2006) Gene expression in blood changes rapidly in neutrophils and monocytes after ischemic stroke in humans: a microarray study. J Cereb Blood Flow Metab 26:1089–1102 doi:10.1038/sj.jcbfm.9600264 CrossRefPubMed Tang Y, Xu H, Du X, Lit L, Walker W, Lu A, Ran R, Gregg JP, Reilly M, Pancioli A, Khoury JC, Sauerbeck LR, Carrozzella JA, Spilker J, Clark J, Wagner KR, Jauch EC, Chang DJ, Verro P, Broderick JP, Sharp FR (2006) Gene expression in blood changes rapidly in neutrophils and monocytes after ischemic stroke in humans: a microarray study. J Cereb Blood Flow Metab 26:1089–1102 doi:10.​1038/​sj.​jcbfm.​9600264 CrossRefPubMed
11.
go back to reference Walker WL, Liao IH, Gilbert DL, Wong B, Pollard KS, McCulloch CE, Lit L, Sharp FR (2008) Empirical Bayes accommodation of batch-effects in microarray data using identical replicate reference samples: application to RNA expression profiling of blood from Duchenne muscular dystrophy patients. BMC Genomics 20:494–501 doi:10.1186/1471-2164-9-494 CrossRef Walker WL, Liao IH, Gilbert DL, Wong B, Pollard KS, McCulloch CE, Lit L, Sharp FR (2008) Empirical Bayes accommodation of batch-effects in microarray data using identical replicate reference samples: application to RNA expression profiling of blood from Duchenne muscular dystrophy patients. BMC Genomics 20:494–501 doi:10.​1186/​1471-2164-9-494 CrossRef
17.
go back to reference Gussoni E, Pavlath GK, Miller RG, Panzara MA, Powell M, Blau HM, Steinman L (1994) Specific T cell receptor gene rearrangements at the site of muscle degeneration in Duchenne muscular dystrophy. J Immunol 153:4798–4805PubMed Gussoni E, Pavlath GK, Miller RG, Panzara MA, Powell M, Blau HM, Steinman L (1994) Specific T cell receptor gene rearrangements at the site of muscle degeneration in Duchenne muscular dystrophy. J Immunol 153:4798–4805PubMed
18.
go back to reference Du X, Tang Y, Xu H, Lit L, Walker W, Ashwood P, Gregg JP, Sharp FR (2006) Genomic profiles for human peripheral blood T cells, B cells, natural killer cells, monocytes, and polymorphonuclear cells: comparisons to ischemic stroke, migraine, and Tourette syndrome. Genomics 87:693–703 doi:10.1016/j.ygeno.2006.02.003 CrossRefPubMed Du X, Tang Y, Xu H, Lit L, Walker W, Ashwood P, Gregg JP, Sharp FR (2006) Genomic profiles for human peripheral blood T cells, B cells, natural killer cells, monocytes, and polymorphonuclear cells: comparisons to ischemic stroke, migraine, and Tourette syndrome. Genomics 87:693–703 doi:10.​1016/​j.​ygeno.​2006.​02.​003 CrossRefPubMed
22.
23.
25.
26.
go back to reference Guzzo RM, Salih M, Moore ED, Tuana BS (2005) Molecular properties of cardiac tail-anchored membrane protein SLMAP are consistent with structural role in arrangement of excitation-contraction coupling apparatus. Am J Physiol Heart Circ Physiol 288:H1810–H1819 doi:10.1152/ajpheart.01015.2004 CrossRefPubMed Guzzo RM, Salih M, Moore ED, Tuana BS (2005) Molecular properties of cardiac tail-anchored membrane protein SLMAP are consistent with structural role in arrangement of excitation-contraction coupling apparatus. Am J Physiol Heart Circ Physiol 288:H1810–H1819 doi:10.​1152/​ajpheart.​01015.​2004 CrossRefPubMed
29.
go back to reference Verde I, Pahlke G, Salanova M, Zhang G, Wang S, Coletti D, Onuffer J, Jin SL, Conti M (2001) Myomegalin is a novel protein of the golgi/centrosome that interacts with a cyclic nucleotide phosphodiesterase. J Biol Chem 276:11189–11198 doi:10.1074/jbc.M006546200 CrossRefPubMed Verde I, Pahlke G, Salanova M, Zhang G, Wang S, Coletti D, Onuffer J, Jin SL, Conti M (2001) Myomegalin is a novel protein of the golgi/centrosome that interacts with a cyclic nucleotide phosphodiesterase. J Biol Chem 276:11189–11198 doi:10.​1074/​jbc.​M006546200 CrossRefPubMed
Metadata
Title
Gene expression in blood of subjects with Duchenne muscular dystrophy
Authors
Brenda Wong
Donald L. Gilbert
Wynn L. Walker
Isaac H. Liao
Lisa Lit
Boryana Stamova
Glen Jickling
Michelle Apperson
Frank R. Sharp
Publication date
01-04-2009
Publisher
Springer-Verlag
Published in
Neurogenetics / Issue 2/2009
Print ISSN: 1364-6745
Electronic ISSN: 1364-6753
DOI
https://doi.org/10.1007/s10048-008-0167-8

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