27 genes offer a molecular diagnosis of heart failure
Scientists working with the National Genome Research Network (NGFN) have now succeeded, for the first time ever, in pinpointing which genes in particular are involved in the late stages of a specific cardiac muscle weakness known as dilatative cardiomyopathy. These genetic blueprints offer tremendous potential for the improved diagnosis and treatment of this complex condition.
Although dilatative cardiomyopathy (DCM) is the main cause of heart failure and heart transplants in the western world, the underlying molecular processes are only partially understood. In everyday clinical practice, BNP (brain natriuretic peptide) has thus far been the only molecular marker available for diagnostic purposes. Its informative value is limited, however, if concomitant diseases are also present.
Dr. Andreas Barth of the University Hospital of Grosshadern in Munich, together with a team led by Dr. Ruprecht Kuner of the German Cancer Research Centre (DKFZ) in Heidelberg, investigated the various genes that are active in healthy and diseased hearts. Using gene chips, they can measure the activity of around 25,000 genes at the same time. In the case of cardiomyopathies, this method is the first to offer NGFN scientists the ability to draw up an informative molecular profile. “We investigated a very large number of samples and established two sets of data in which the samples came either from the partition wall of the cardiac muscle or from the left ventricle of healthy hearts or hearts demonstrating cardiac insufficiency. This means we can be sure that the differences in gene activity are actually a result of the disease and are not caused by biological variations in the tissue," says Barth. In both cases, the scientists observed that, in the tissue of patients with the disease, four to five times more genes were active than in those with healthy hearts. “Heart failure therefore appears to be linked to significant gene activation,” concludes Barth. Some genes were however also less active in the diseased tissue than in the intact heart muscle.
Barth and Kuner finally identified a set of 27 genes that can be used to distinguish diseased hearts from healthy ones with a sensitivity of over 90 per cent. Over the course of their experiments, they tested a total of 108 samples of cardiac muscle. The gene set also includes known markers such as BNP. “This means that late–stage DCM can be reliably identified for the first time at molecular level”, says Barth. He hopes that these results will help improve the treatment of patients with heart failure.
Website of scientists involved in this NGFN projectUniversity Hospital Munich-Großhadern
German Cancer Research Center (DKFZ)
Ludwig-Maximilian-University Munich
