Mayo's study of family finds genetic root to heart flaw

The discovery of a mutation that causes irregular heartbeat raises hopes for a treatment.

By J OSEPHINE MARCOTTY

Last update: July 11, 2008 - 10:03 AM

Researchers at the Mayo Clinic in Rochester have discovered a new genetic mutation that leads to the most common kind of chronic irregular heart beat, a dangerous condition that can cause stroke or sudden death.

Atrial fibrillation affects 2.2 million Americans. By studying one large family that shared the condition, researchers found a defective gene never before linked to the disease. In that family it creates an abnormal hormone that makes the heart beat too fast and irregularly.

The condition is a prime area for research using the human genome to sleuth the genetic roots of disease. With atrial fibrillation, there are drugs that can sometimes help the condition. But they often don't work, especially in people with the inherited version. In severe cases surgeons destroy the area of the heart where the electrical disruption begins, said Dr. Timothy Olson, the lead researcher.

Once scientists can pinpoint what process in the body is triggered by the defective gene, then they hope they can come up with ways to stop it, Olson said.

"Ultimately, we may be able to develop a treatment that specifically targets the underlying defect," he said.

Most people with atrial fibrillation develop it as a result of old age and diseased hearts. Researchers have known that those with atrial fibrillation relatively early in life - about 10 percent of the total -- have a hereditary susceptibility to it. They inherit abnormal genes that interfere with how their heart cells process sodium and potassium, elements that regulate electrical activity in the heart.

In atrial fibrillation that syncopated electrical activity goes haywire. Sometimes, the heart stops beating altogether, leading to sudden death.

But researchers found that this family, which was not identified, developed the disease in a unique way. The abnormal hormone, which the body uses to regulate salt levels in the blood among other things, somehow disrupts the electrical system in the heart. Olson said that the discovery means that any number of faulty genes could lead to the same disease through a variety of biological pathways.

"We are looking at the tip of the iceberg in those genes that have been identified," Olson said.

The study was reported in today's New England Journal of Medicine.

This family was one of 50 that Olson and his co-researchers are following in a broader effort to better understand the genetic basis of atrial fibrillation. It is an example of a relatively recent type of medical research brought about by the unraveling of the human genome. Olson is doing similar research in families who develop enlarged hearts.

"There is not a day that goes by without the discovery of a genetic factor that contributes to diabetes or hypertension or some of the behavioral disorders like schizophrenia or autism," said Dr. Harry Orr, director of the Institute of Human Genetics at the University of Minnesota.

When those discoveries also include the discovery of new pathways that lead to disease, researchers get excited, he added. Ultimately, they hope that they will also lead to new treatments and drugs that interfere somehow with the process of the disease.

"But that is more promise than product right now," he said.

Josephine Marcotty • 612 673 7394

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