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Researchers discover a genetic cause for atrial fibrillation

21.07.2006
Mayo Clinic investigators have discovered a gene mutation causing chaotic electrical activation of the heart muscle and atrial fibrillation (AF), a common heart-rhythm disturbance affecting millions of Americans. Atrial fibrillation can lead to heart failure and stroke.

"The discovery underscores the significance of heredity in susceptibility to atrial fibrillation," explains Timothy M. Olson, M.D., director of the Cardiovascular Genetics Laboratory at Mayo Clinic.

"Identification of a new molecular basis for atrial fibrillation provides a critical step toward individualized diagnosis and treatment of arrhythmia," adds Andre Terzic, M.D., Ph.D., director of Mayo Clinic's Marriott Heart Disease Research Program.

The Mayo Clinic discovery is published in the July 15 issue of the journal Human Molecular Genetics (http://hmg.oxfordjournals.org/cgi/

content/full/15/14/2185).

Significance of the Mayo Clinic Research

The Mayo Clinic study provides new insight into a previously unrecognized mechanism for electrical instability in the human heart. The Mayo multidisciplinary team is the first to identify a specific genetic mutation of the ion channel gene KCNA5 that leads to a disease-causing condition called a channelopathy.

A channelopathy is an abnormality of specific miniature transportation tubes in cell membranes. The job of these tubes -- or channels -- is to selectively allow certain charged particles in and out of the cell, and in this way, pass electrical currents in and out of the cell to regulate each heartbeat. The KCNA5 mutation causes loss of function of an atrial-specific potassium ion channel, disrupting electrical synchronization. This leads to susceptibility for atrial fibrillation.

About Atrial Fibrillation

Atrial fibrillation is the most common arrhythmia -- or irregular heartbeat -- worldwide. In the United States alone, more than 2 million Americans suffer from atrial fibrillation, constituting a major public health epidemic. During a person's lifetime, there is a 25 percent risk this rhythm disorder will develop, and patients with atrial fibrillation have a fivefold increased risk for stroke. Atrial fibrillation has been increasingly recognized as an inherited disease.

About the Study

The Mayo investigation used comprehensive genetic analysis to identify a mutation in the DNA of a sibling pair with atrial fibrillation in the absence of known risk factors for the disease. This genetic anomaly was not present in the DNA of individuals without atrial fibrillation.

The atrial fibrillation mutation occurred in the KCNA5 gene, which produces a key heart protein known as Kv1.5. Loss of Kv1.5 function, in turn, made the atria -- the upper pumping chambers of the heart -- more vulnerable to stress-induced chaotic rhythms, and atrial fibrillation.

To validate the finding, the researchers reproduced the disease features at the molecular, cellular and organism levels and corrected the mutation, restoring the defective ionic current.

Traci Klein | EurekAlert!
Further information:
http://www.mayo.edu
http://hmg.oxfordjournals.org/cgi/content/full/15/14/2185

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