Study IDs Gene Variants Tied to Sudden Cardiac Death

MONDAY March 23, 2009 -- Fourteen common genetic variants associated with a risk factor for sudden cardiac death have been identified by researchers who analyzed genetic data from more than 13,000 people.

The gene variants they identified influence the QT interval measured on electrocardiograms (EKGs) routinely used by doctors to assess patients' heart health. The QT interval is the time from the beginning of electrical activation of the heart to the end of electrical relaxation, according to background information in a news release about the study.

The researchers said their findings, published online in Nature Genetics, could help prevent heart arrhythmia and prevent sudden cardiac death by limiting the use of medications that affect QT interval in people with these 14 gene variants, which are located in 10 different gene regions.

"It is well-established that prolongation of the QT interval in the general population is a potent and heritable risk factor for sudden death. In addition, QT prolongation results from medications leading to drug-induced cardiac arrhythmias and sudden death. This is a cardiotoxic side effect of scores of medications in widespread use and has been a major barrier to the development of novel drugs," study author Dr. Christopher Newton-Cheh, of the Massachusetts General Hospital (MGH) Center for Human Genetic Research and Cardiovascular Research Center, said in an MGH news release.

"From studies of families with congenital long-QT syndrome, we know that rare mutations with strong effects on ion channel function lead to QT prolongation and sudden death. But the common genetic basis for QT prolongation has been very difficult to establish," he said.

A companion study in the same issue of Nature Genetics looked at more than 15,000 people and confirmed 12 of the 14 variants identified in the first study. It also identified two additional gene regions.

"We were very reassured to see such strong replication in two independent studies," Newton-Cheh said.

While a combination of risk factors -- such as heart disease, older age, being female and use of other medications -- contributes to drug-induced arrhythmias, "it is certainly possible that common genetic variants will add incrementally to risk prediction, " he said.

But, Newton-Cheh added, it's "premature to advocate screening gene variants for risk assessment, but someday it may be possible to identify individuals who are particularly high risk and should avoid" medications that can cause QT prolongation.

More information

The U.S. National Heart, Lung, and Blood Institute has more about long QT syndrome.

Posted: March 2009


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