A new study shows that atrial fibrillation - the most common form of sustained heart arrhythmia - can be caused in an unexpected way.
Researchers report in the December 12th issue of the journal Cell, a Cell Press publication, the first evidence that a rare and particularly severe form of the disease stems from a gene involved in shuttling other molecules in and out of the cell nucleus, where the DNA that serves as the blueprint for life is housed.
"The common thinking is that atrial fibrillation is an electrical problem of the heart," said Qing Kenneth Wang of the Cleveland Clinic. That has led to the notion that ion channels are primarily responsible since they control the electrical impulses that keep the heart beating.
Wang's team now shows that defects in a gene known as NUP155, a key component of the so-called nuclear pore complex, also leads to arrhythmia in patients with two abnormal copies of the gene. "It's unexpected," he said. "We never thought a gene like this could lead to atrial fibrillation."
Atrial fibrillation is characterized by uncoordinated beating of the hearts upper chambers. The heartbeat in patients with atrial fibrillation is not only uncoordinated, Wang said, but also very chaotic and rapid. Whereas a normal heart beats 70 or 80 times a minute, in atrial fibrillation that rate can jump to 300 beats per minute. As the population ages, the incidence of the disease is rising in step and atrial fibrillation is now responsible for an estimated 15 percent of all strokes.
In most people, the disease stems from a complex interplay of genetic and environmental causes. In some 30 percent, however, the disease is tied directly to single genes that are passed down over generations, spurring disease in some cases with a single abnormal copy and in others only in those with two defective variants. In a handful of families, those rare genes have been linked to ion channels, but in many cases the function of the genes responsible remains a mystery.
Wang's team had earlier traced the gene responsible for atrial fibrillation in one family to a region on chromosome 5. Family members with two copies of the offending variant develop symptoms of the disease and can suffer sudden death in early childhood. They now find that the root cause is NUP155.