Functional Genomics - Gene expression profiling Transcriptome of monocytes

Coordinator:		Prof. Dr. Stefan Blankenberg, Dr. Patrick Diemert
Institution:		Universitätsmedizin Mainz
Homepage:		www.klinik.uni-mainz.de

The aim of this project was the identification of genes whose expression is altered under conditions of subclinical atherosclerosis or acute myocardial infarction and is thus involved in the predisposition to subclinical atherosclerosis or in the pathophysiology of myocardial infarction. Together with results of studies on the genetic variability information on the gene level (DNA) and gene expression levels (RNA) might help to improve cardiovascular risk assessment. In addition, an improvement in the understanding of the pathomechnisms of the disease through the study of gene expression and the involvement of miRNAs was expected.
Various genexpressions-/eQTL analyses were carried out in the framework of this project, which included the analysis of microRNAs and circulating miRNAs as well as the differential gene expression in young myocardial infarction patients.
To evaluate the potential of miRNAs as diagnostic marker for myocardial infarction, circulating miRNA concentration in the serum of patients with myocardial infarction was determined by TaqMan technology and analyzed in comparison to control samples (without myocardial infarction). It was possible to identify miRNAs that are specifically increased or decreased in the presence of a heart attack. A validation these results was performed in additional independent studies.
Furthermore, a gene expression analysis was carried out to identify genes whose expression is altered in patients with myocardial infarction. A group of patients who suffered myocardial infarction at a young age (under 50 years) were compared with a control group, which was matched according to the age and sex. In these analyses genes were identified as differentially regulated, which play an important role in lipid metabolism and signal transduction. Currently, these genes are analyzed in the laboratory in more detail. Using the data generated as part of this project a large consortium, the MetaXpress consortium was formed, which deals with the methodological and technical aspects of standardization and joint analyses of gene expression data. Partners in this consortium are the three large population-based studies Gutenberg Health Study (Mainz / Hamburg), the SHIP Study (Greifswald) and the KORA Study (Augsburg / Munich).