| P228 | CardioChip: Diagnostic Profiling for Myocardial Patients. |
| 1T.Storm, 1D.Weichenhan, 2H.Witt, 1J.Jäger, 2M.Drungowski, 1B.Ivandic, 2P.Ruiz, 1H.Katus | |
| 1Universitätsklinikum Heidelberg, Medizinische Klinik III Bergheimer Str. 58, Heidelberg; 2Max-Planck-Institut für Molekulare Genetik, Ihnestr. 73, Berlin. | |
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Cardiomyopathies are characterized by ventricular hypertrophy or dilation and are associated with diastolic or systolic dysfunction, respectively. While about 50% of patients with hypertrophic cardiomyopathies display autosomal dominant inheritance, only some 30% of the dilated cases can be ascribed to a familial etiology. The individual genetic background may substantially affect development, progression, and outcome of the disease. Our work is directed at implementing a microarray for diagnostic and pharmacogenetic expression profiling of cardiomyopathy patients. In a first step, we hybridized pooled RNA from 60 diseased and control cardiac tissues to human Unigene set II (RZPD 2). We found ~11,300 transcripts to be expressed in the heart. These were rearrayed to produce CardioChip 1 (CC1), which we are using to obtain individual expression fingerprints for >90 specimens from healthy controls and stable, non-terminal patients. The latter had been diagnosed with either hypertrophic (obstructive/non-obstructive) or dilated cardiomyopathy, or rheumatoid arthritis with myocardial affection. In addition, we have established high-throughput TaqMan PCR screening for a number of known mutations in cytoskeletal genes that can be regarded as cardiomyopathy markers. The correlation of genotypes with clinical and expression data shall improve phenotype classification and allow for tailoring and monitoring of patient-specific therapies. Moreover, CC1 will serve as a valuable research tool to explore the complex signalling pathways associated with pathogenesis in cardiac muscle. For routine diagnostics, a second-generation CardioChip is going to be developed based on our experimental data. |