Two international research studies, both led by investigators affiliated with Massachusetts General Hospital (MGH) and the Broad Institute of MIT and Harvard, have uncovered new information about genes that may increase the risk of serious cardiac arrhythmias. The studies recently received back-to-back advance online publication in Nature Genetics and Nature Methods.
The Nature Genetics report identifies several new gene regions associated with variations in the QT interval a stage in the heart's electrical cycle that, if prolonged, increases the risk of drug-induced arrhythmias and sudden cardiac death. A surprising finding of that paper was the extent to which genes involved in calcium signaling influence the QT interval, the time from electrical activation of heart cells, which stimulates contraction, to the end of electrical relaxation.
"We have known that calcium signaling is critically important in regulating the contraction of muscle cells that generates the heartbeat," says Christopher Newton-Cheh, MD, MPH, of the MGH Center for Human Genetic Research and Cardiovascular Research Center, corresponding and co-senior author of the Nature Genetics report. "But finding that calcium is also involved in resetting the heart after each beat was a total surprise and represents a new avenue to pursue in the causes of arrhythmias."
The Nature Methods paper describes a novel approach to analyze and map the protein networks that drive cardiac repolarization the biological process disturbed in arrhythmias. By integrating this network with results from the Nature Genetics paper, the researchers were able to pinpoint specific genes involved in the biology of cardiac repolarization, which would have been challenging to accomplish from the genetics alone. This approach also allowed identification of three genetic variants involved in arrhythmias that had been missed in earlier studies.
|Contact: Sue McGreevey|
Massachusetts General Hospital