Using a new genomic strategy that has the power to survey the entire human genome and identify genes with common variants that contribute to complex diseases, researchers at Johns Hopkins, together with scientists from Munich, Germany, and the Framingham Heart Study, U.S.A., have identified a gene that may predispose some people to abnormal heart rhythms that lead to sudden cardiac death, a condition affecting more than 300 thousand Americans each year.

The gene called NOS1AP, not previously flagged by or suspected from more traditional gene-hunting approaches, appears to influence significantly one particular risk factor - the so-called QT interval length - for sudden cardiac death. The work will be published online at Nature Genetics on April 30.

"In addition to finding a genetic variant that could be of clinical value for sudden cardiac death, this study also demonstrates how valuable large-scale genomics studies can be in detecting novel biological targets," says the study's senior author, Aravinda Chakravarti, Ph.D., director of the McKusick-Nathans Institute for Genetic Medicine at Hopkins. "This study, conducted during the early days of a new technology, would have been impossible without the pioneering support of the D.W. Reynolds Foundation in their generous support of our clinical program in sudden cardiac death here at Hopkins."

QT interval measures the period of time it takes the heart to recover from the ventricular beat - when the two bottom chambers of the heart pump. Corresponding to the "lub" part of the "lub-dub" pattern of the heartbeat, an individual's QT interval remains constant. This interval is partly dependent on one's genetic constitution and, moreover, genes also play a role in sudden cardiac death.

"There's a great deal of evidence out there that having a too long or too short QT interval is a risk factor for sudden cardiac death," says the study's co-first author, Dan Arking, Ph.D., an instructor in the
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Contact: Audrey Huang
audrey@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
30-Apr-2006

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