April 2, 2009
Genetic variants associated with sudden cardiac death
Researchers have located nine new genetic variants, and confirmed the role of another recently identified variant, that affect the time that it takes for the heart to reset itself after each beat. The duration of this QT interval, as it is called, is routinely measured by electrocardiogram (EKG). A lengthened QT interval is a known risk factor for sudden death. The results were published recently in the journal Nature Genetics.
The international team of researchers, part of the QTGEN Consortium, studied 15,842 people enrolled in the UW-coordinated Cardiovascular Health Study, the Massachusetts-based Framingham Study, and the Rotterdam Study in The Netherlands. These are all long-term studies of thousands of adults whose heart health has been tracked for decades. The study’s analysis showed that the more of these genetic risk variants a person had, the more likely a QT interval problem was present.
Some people with too long or too short QT intervals are vulnerable to life-threatening heart rhythm disturbances. This can happen at any age, even in young, apparently healthy, fit athletes.
Some also are prone to medication-induced cardiac arrests. A wide variety of medications, including drugs that treat other heart rhythm problems, can provoke a cardiac arrest in people with abnormal QT intervals.
“It’s very difficult for physicians to predict who is at risk for sudden cardiac death or drug-induced ventricular arrhythmias,” said one of the lead authors of the study, Kenneth Rice, assistant professor of biostatistics at the UW School of Public Health and Community Medicine. In most cases the heart just stops beating without any warning.
There are some known risk factors, such as female gender, fainting episodes after physical activity or emotional excitement, and a family history of deaths during exercise or unexplained deaths in otherwise healthy relatives.
“But we’re interested in finding the actual genes that predispose people to sudden cardiac death, in order to have more specific predictors,” Rice said.
Surprisingly, almost half of the newly discovered genetic variants were in areas of the genome not previously associated with heart rhythm disturbances.
“There’s still a lot more work to be done to figure out how these genetic variants affect the underlying biology of the heart,” Rice said. “We now know their location on the genome, but researchers still need to figure out the mechanisms affected by these variants.”
Rice explained, “The technology to study genomes has recently improved in leaps and bounds. The research that can be done now is quite different in scale and approach to just a few years ago. Today we can analyze data from thousands of individuals, all the way along their genomes. Instead of having to concentrate only on genes where we believe we might find something, we can now simply look to see whatever is out there.”
Rice said that, because of this genetic revolution in epidemiology — the study of the rates and risks illnesses in large populations — people can expect to see more reports soon on discoveries of genetic variants for conditions related to heart and blood vessel disease, such as high blood pressure, stroke, diabetes, and obesity.
Other UW epidemiologists, cardiologists, and biostatisticians in the international, multi-center study of abnormal QT interval genetics were Joshua Bis, Kristin Marciante, Nona Sotoodehnia, Nicholas L. Smith, Susan R. Heckbert, Bruce M. Psaty, and Thomas Lumley. Smith is also with the Veterans Administration Office of Research and Development in Seattle.
