Mutant Gene May Help Cause Abnormal Heartbeat

The finding could explain many cases of atrial fibrillation

WEDNESDAY, June 21, 2006 (HealthDay News) -- A genetic flaw may help trigger atrial fibrillation, the dangerous abnormal heartbeat whose cause has long remained a mystery.

Canadian researchers say mutations in a gene for a protein called connexin 40, which transmits the electrical signals that keep the heart beating normally, were found in 4 of 15 patients with atrial fibrillation classified as "idiopathic" -- meaning no specific cause could be found.

"This study confirms that connexin 40 is critical for normal electrical conductivity," said Dr. Michael H. Gollob, an assistant professor of medicine at the Ottawa Heart Institute and lead author of the report. "It is a very important protein. This study suggests that connexin 40 should be considered as a target for new drugs to treat atrial fibrillation."

Gollob's team published its findings in the June 22 issue of the New England Journal of Medicine.

Atrial fibrillation affects the two upper chambers of the heart. It is not as deadly as ventricular fibrillation, which affects the lower chambers. Still, it remains a leading risk factor for stroke because the irregular rhythm can cause blood to pool, raising risks for clots that can pass to the brain.

According to Dr. Jeffrey E. Saffitz, professor of pathology at Harvard Medical School, who wrote an accompanying editorial, atrial fibrillation "is a very common arrhythmia, particularly in the elderly. The risk is 100 times greater when you are 80 than when you are 40."

Until now, there have been only a few scattered reports of a genetic abnormality involved with atrial fibrillation, Gollob said. Most of these reports were based on studies of families in which the condition recurred frequently. The new study looked at patients for whom there was no hint of a familial tie.

The study also used a decidedly unconventional method. Researchers usually look for genetic mutations in blood cells called lymphocytes, assuming that a mutation will pop up in all of the body's cells. But the connexin 40 mutations were found only in heart cells, not in lymphocytes, Gollob noted.

"We only identified the mutations when we looked at the diseased tissue," he said. "Now we can say that atrial fibrillation can be genetic in origin, but it can only be identified by looking at diseased tissue."

The mutations probably are present from birth, Gollob said. They come into play as someone grows older, tipping the cardiac balance toward atrial fibrillation.

"This study gives us a more nuanced understanding of atrial fibrillation," Saffitz said. "It may help explain why some people develop atrial fibrillation and others do not."

But the discovery also has much wider implications, Gollob said.

"This supports a very novel view," he said. "It says that idiopathic diseases of all sorts may have a genetic basis, and that their origin can be detected by looking at diseased tissues."

For his part, Saffitz said the finding offers an important insight into a number of genes and changes in genes. He believes experts will now have to consider genetic factors as important determinants of atrial fibrillation.

More information

Find out more about atrial fibrillation at the American Heart Association.

SOURCES: Michael H. Gollob, M.D., assistant professor, medicine, Ottawa Heart Institute, Canada; Jeffrey E. Saffitz, M.D., Ph.D., professor, pathology, Harvard Medical School, Boston; June 22, 2006, New England Journal of Medicine
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