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Genetic risk factors identified for sudden cardiac death

Building on these findings, the Helmholtz scientists and their clinical partners want to obtain further insights into the pathogenesic mechanisms of the disease and gain perspectives for early diagnosis and therapy. The results of the genome-wide study have been published online in the journal Nature Genetics.

Together with scientists of the international research consortium QTSCD (QT Interval and Sudden Cardiac Death), Dr. Arne Pfeufer of the Institute of human Genetics at Helmholtz Zentrum Mnchen has identified 10 gene variants which predispose to an elevated risk for arrhythmias and SCD. In interaction with other, still undiscovered factors, these gene variants influence heart repolarization and raise or lower the risk of cardiac arrhythmias. In their study, the scientists examined the electrocardiograms of more than 15,000 persons from Germany, Italy and the U.S.

"The results of a second science consortium, QTGEN, were nearly identical to our findings," said Pfeufer. This provides assurance for the scientists involved in the study the Munich research team led by Professor Thomas Meitinger, institute director at Helmholtz Zentrum Mnchen and holder of the chair in human genetics at the Technische Universitt Mnchen (TUM) and Assistant Professor Stefan Kb, MD, senior physician at the University Hospital of Munich, Campus Grosshadern, along with their German, Italian and American colleagues that their approach was correct and that the findings are absolutely reliable.

"For clinicians, an important indicator for increased arrhythmia risk is the QT interval in the ECG," Stefan Kb explained. The QT interval describes the time span needed to send the electrical impulse into the heart ventricles and then to recharge. A prolonged QT interval can depending on the underlying disease increase the risk of arrhythmias and SCD up to five-fold.

The scientists were not looking for rare variants carried by only a few people. Rather, they were particularly interested in common gene variants, which in each person can influence the length of the QT interval. They do not increase the personal disease risk as single genes, but rather in combination of genetic factors and in context with other risk factors such as medications or ischemia.

"We view this form of genome-wide search for common gene variants associated with widespread diseases as a very promising approach for making discoveries in totally uncharted territory," said Thomas Meitinger, describing the method. "In contrast to the study of single genes, this genome-wide approach offers entirely new starting points for the investigation of common diseases such as sudden cardiac death."

The provision of highly valid population-based data of test persons from the KORA study platform headed by Professor H.-Erich Wichmann, director of the Institute of Epidemiology at Helmholtz Zentrum Mnchen, formed an essential basis for the successful realization of the research project.

The QTSCD study arose from long-standing close collaboration between human geneticists, cardiologists, epidemiologists and informaticians of Helmholtz Zentrum Mnchen, the university hospital Klinikum rechts der Isar of the Technische Universitt Mnchen and the university hospital of Ludwig Maximilian University (LMU), Campus Grosshadern. Other partners of Helmholtz Zentrum Mnchen in the QTSCD consortium were the scientists of the Heinz Nixdorf RECALL Study in Essen and the research center Life & Brain of the University of Bonn. Professor Aravinda Chakravarti of John Hopkins University in Baltimore was director of the project.

In a next step, follow-up studies shall confirm the connection between the new gene variants and sudden cardiac death. "We want to collect and evaluate further data on the respective individual genetic risk for arrhythmias in a large number of patients," Dr. Kb said. The common objective of the Helmholtz scientists and their clinical partners through these studies is to gain further insights into pathogenetic mechanisms and thus gain perspectives for improved risk prediction and more successful therapy.


Contact: Sven Winkler
Helmholtz Zentrum Mnchen - German Research Center for Environmental Health

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