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Ten genes identified in connection with sudden cardiac death

ANN ARBOR, Mich.---You're sitting at your desk and suddenly your heart is beating in overdrive or worse, lurching along like a car on fumes. It is a shocking, uncomfortable and frightening sensation.

Irregular heart rhythms are a common cause of sudden cardiac death or SCD, a condition that accounts for 450,000 deaths annually in the United States. Scientists are now closer to understanding what causes SCD and who it may strike, said Gonalo Abecasis, associate professor of biostatistics at the University of Michigan School of Public Health.

Abecasis co-led on an international study aiming to identify genetic defects associated with sudden cardiac death. Aravinda Chakravarti of Johns Hopkins and Arne Pfeufer of the Institute for Human Genetics in Germany also co-led the study. Serena Sanna, formerly at the U-M School of Public Health and now a researcher at the National Research Center in Cagliari, Italy, was joint first author.

The team identified 10 genes associated with changes in the so-called QT interval duration. The QT interval duration measures the length of time the heart takes to contract. A QT interval that's too long or too short can cause serious problems, including arrhythmias and sudden cardiac death. The QT interval can be seen on an electrocardiogram monitor; it's a certain portion of the line that waves or spikes up and down when the heart contracts.

The genes are interesting for several other reasons, Abecasis said. Changes in the QT interval are one of the common side effects that lead pharmaceutical companies to cancel new drugs that are under development, Abecasis said. This discovery could help identify individuals most at risk of that complication and, eventually, help the industry develop drugs that avoid that complication altogether.

The genes also confirm existing medical theory. A number of the 10 genes help regulate human potassium channels in the heart muscle, reinforcing the idea that the balance of sodium and potassium moving in and out of the heart muscle is important, Abecasis said. "There's a couple where we don't really now what they do, so we're hoping maybe they will give us an interesting lead into other things.

"Each gene we identified can produce a small alteration in the QT interval," Abecasis said. "Individuals with too many genes predisposing to a long or short QT interval are likely to be most at risk of sudden cardiac death."

The next research phase will follow people over time and see which carriers have SCD or are at most risk, and how the changes in QT interval translate into changes in risk, Abecasis said.

Scientists studied DNA and electrocardiograms for 15,000 people, and contrasted their findings with those of a parallel study of similar size led by Chris Newton Cheh of the Broad Institute.


Contact: Laura Bailey
University of Michigan

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