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Gene mingling increases sudden death risk
Date:10/12/2009

A multi-national research team has discovered that two genetic factors converge to increase the risk of sudden cardiac death.

The investigators from the United States, Italy and South Africa report in the journal Circulation that variations in the gene NOS1AP increase the risk of cardiac symptoms and sudden death in patients who have an inherited cardiac disease called congenital long-QT syndrome.

The findings will help in assessing the risk of sudden death and assigning therapy in patients with this syndrome, said senior author Alfred George Jr., M.D., director of the Division of Genetic Medicine at Vanderbilt University Medical Center.

Congenital long-QT syndrome affects the electrical activity of the heart ("QT" refers to a time measure on the electrocardiogram it is longer than normal in patients with the syndrome). Long-QT syndrome makes patients susceptible to potentially fatal disorders of heart rhythm. It is a known cause of sudden death, especially in young adults and children, and has recently been estimated to affect about one in 2,200 individuals.

But not all people who have gene mutations that cause congenital long-QT syndrome have symptoms (fainting, cardiac arrest, sudden death). The big question mark, George said, is how to manage a patient who has a long-QT gene mutation, but doesn't have any symptoms.

"The concern of course is that the first symptom could be sudden death," he said. "And everything needs to be done to try to prevent that.

"But does every mutation carrier need an implantable defibrillator? Pharmacological therapies? Or should they just be watched?"

The variability in symptoms suggests that other factors play a role either to promote or prevent symptoms.

George and Peter Schwartz, M.D., at the University of Pavia, Italy, have collaborated over the last seven years to search for "genetic modifiers" of long-QT syndrome genes other than the disease-causing
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Contact: Leigh MacMillan
leigh.macmillan@vanderbilt.edu
615-322-4747
Vanderbilt University Medical Center
Source:Eurekalert

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