HOME SUBSCRIPTIONS CURRENT ISSUE PAST ISSUES CARDIOSOURCE SEARCH HELP FEEDBACK		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) View Expanded Materials and Methods All Versions of this Article: j.jacc.2006.07.026v1 48/8/1610    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Barth, A. S. Articles by Sültmann, H. Search for Related Content PubMed PubMed Citation Articles by Barth, A. S. Articles by Sültmann, H.

CLINICAL RESEARCH: HEART FAILURE

Identification of a Common Gene Expression Signature in Dilated Cardiomyopathy Across Independent Microarray Studies

Andreas S. Barth, MD^_*,_*, Ruprecht Kuner, PhD, Andreas Buness, MSc, Markus Ruschhaupt, MSc^,, Sylvia Merk, DVM^,||, Ludwig Zwermann, MD^_*, Stefan Kääb, MD^_*, Eckart Kreuzer, MD, Gerhard Steinbeck, MD^_*, Ulrich Mansmann, PhD, Annemarie Poustka, PhD, Michael Nabauer, MD^_* and Holger Sültmann, PhD

^_* Department of Medicine I, University Hospital Grosshadern, Munich, Germany
Department of Cardiac Surgery, University Hospital Grosshadern, Munich, Germany
Department of Medical Informatics, Biometrics and Epidemiology, Ludwig-Maximilians-University, Munich, Germany
Division of Molecular Genome Analysis, German Cancer Research Center, Heidelberg, Germany
^|| Department of Medical Informatics and Biomathematics, University of Münster, Münster, Germany

Manuscript received December 18, 2005; revised manuscript received April 14, 2006, accepted June 6, 2006.

^_* Reprint requests and correspondence: Dr. Andreas S. Barth, Department of Medicine I, University Hospital Grosshadern, Munich, Marchioninistrasse 15, 81377 Munich, Germany (Email: andreas.barth{at}med.uni-muenchen.de).

OBJECTIVES: This study was designed to identify a common gene expression signature in dilated cardiomyopathy (DCM) across different microarray studies.

BACKGROUND: Dilated cardiomyopathy is a common cause of heart failure in Western countries. Although gene expression arrays have emerged as a powerful tool for delineating complex disease patterns, differences in platform technology, tissue heterogeneity, and small sample sizes obscure the underlying pathophysiologic events and hamper a comprehensive interpretation of different microarray studies in heart failure.

METHODS: We accounted for tissue heterogeneity and technical aspects by performing 2 genome-wide expression studies based on cDNA and short-oligonucleotide microarray platforms which comprised independent septal and left ventricular tissue samples from nonfailing (NF) (n = 20) and DCM (n = 20) hearts.

RESULTS: Concordant results emerged for major gene ontology classes between cDNA and oligonucleotide microarrays. Notably, immune response processes displayed the most pronounced down-regulation on both microarray types, linking this functional gene class to the pathogenesis of end-stage DCM. Furthermore, a robust set of 27 genes was identified that classified DCM and NF samples with >90% accuracy in a total of 108 myocardial samples from our cDNA and oligonucleotide microarray studies as well as 2 publicly available datasets.

CONCLUSIONS: For the first time, independent microarray datasets pointed to significant involvement of immune response processes in end-stage DCM. Moreover, based on 4 independent microarray datasets, we present a robust gene expression signature of DCM, encouraging future prospective studies for the implementation of disease biomarkers in the management of patients with heart failure.

Abbreviations and Acronyms   DCM = dilated cardiomyopathy   GO = Gene Ontology   ICM = ischemic cardiomyopathy   NF = nonfailing

This article has been cited by other articles:

				R. Kuner, A. S. Barth, M. Ruschhaupt, A. Buness, L. Zwermann, E. Kreuzer, G. Steinbeck, A. Poustka, H. Sultmann, and M. Nabauer Genomic analysis reveals poor separation of human cardiomyopathies of ischemic and nonischemic etiologies Physiol Genomics, June 10, 2008; 34(1): 88 - 94. [Abstract] [Full Text] [PDF]

				G. E. Haddad, L. J. Saunders, S. D. Crosby, M. Carles, F. del Monte, K. King, M. R. Bristow, F. G. Spinale, T. E. Macgillivray, M. J. Semigran, et al. Human cardiac-specific cDNA array for idiopathic dilated cardiomyopathy: sex-related differences Physiol Genomics, April 21, 2008; 33(2): 267 - 277. [Abstract] [Full Text] [PDF]

				A. O. Gramolini, T. Kislinger, R. Alikhani-Koopaei, V. Fong, N. J. Thompson, R. Isserlin, P. Sharma, G. Y. Oudit, M. G. Trivieri, A. Fagan, et al. Comparative Proteomics Profiling of a Phospholamban Mutant Mouse Model of Dilated Cardiomyopathy Reveals Progressive Intracellular Stress Responses Mol. Cell. Proteomics, March 1, 2008; 7(3): 519 - 533. [Abstract] [Full Text] [PDF]

				G. S. Ginsburg, D. Seo, and C. Frazier Microarrays Coming of Age in Cardiovascular Medicine: Standards, Predictions, and Biology J. Am. Coll. Cardiol., October 17, 2006; 48(8): 1618 - 1620. [Full Text] [PDF]