McGowan Institute faculty member Barry London, MD, PhD, the Harry S. Tack professor of medicine and chief, division of cardiology at the University of Pittsburgh School of Medicine, and director of the University of Pittsburgh Medical Center (UPMC) Cardiovascular Institute, and his colleagues have identified a new gene responsible for a rare, inherited form of sudden cardiac arrest, known as Brugada syndrome. With the identification of this new gene, the researchers hope this finding will shed light on the more common forms of sudden death in patients with heart attacks and heart failure, and will help aid in the development of new, effective therapeutic treatments that will prevent all types of fatal arrhythmias.
Brugada syndrome is a rare inherited arrhythmia, which is more commonly symptomatic in males. It can present with an abnormality on the electrocardiogram (ECG), fainting, or sudden death. In about 20 percent of patients with Brugada syndrome, mutations in the heart’s sodium channels lead to less current flow and shorter heart beats in a part of the heart. This puts patients at risk for rapid heart rhythms such as ventricular tachycardia and fibrillation. Symptoms often present with no warning, and the seemingly healthy patient passes out and/or suffers a sudden cardiac arrest from an arrhythmia.
“In this study we found that GPD1-L, while not an ion channel itself, is a trafficking gene that allows the sodium channel to find its way to the cell membrane. The mutation interferes with the trafficking and leads to potentially fatal arrhythmias,” said Dr. London. “Equally important, we suspect that the function of the native GPD1-L gene and the mutant are influenced by oxidative stress, a process which interferes with the body’s natural ability to repair itself from antioxidant assaults, e.g., pollution, smoking, or stress. Also, patients with Brugada syndrome only rarely have symptoms; they have this genetic mutation all the time. So, the question now is, why do arrhythmias or sudden death happen on any one particular day? Something else is happening concurrently with this mutation to trigger the potentially lethal rhythm problems. With the identification of this new GPD1-L gene, we hope to identify other new genes along with entirely new pathways that stabilize the rhythm of the heart, increasing our understanding of the mechanisms that lead to sudden death in this particular condition,” added Dr. London.
Arrhythmias remain a major public health problem leading to more than 250,000 sudden cardiac deaths each year. Brugada syndrome was only identified approximately 15 years ago and much is still not understood about the condition. It is found all over the world and presently there is no cure. The best therapy to date is to implant a defibrillator into the chests of patients who are clinically found to be at high risk.
Illustration: McGowan Institute for Regenerative Medicine.
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Abstract (Circulation. 2007; doi: 10.1161/CIRCULATIONAHA.107.703330)