University of Iowa researchers and colleagues in France have identified a gene variant that causes a potentially fatal human heart rhythm disorder called sinus node disease. Also known as "sick sinus syndrome," the disease affects approximately one in 600 heart patients older than 65 and is responsible for 50 percent or more of the permanent pacemaker placements in the United States.
While the newly discovered gene variant is rare, the study provides insight into cellular mechanisms that regulate sinus node function and identifies an unanticipated new pathway for developing future therapies to regulate more common forms of sinus node disease. The findings, which also have research implications beyond heart disease, were published online Oct. 1 by the Proceedings of the National Academy of Sciences.
The team first analyzed data from two families in France: a family of 74 individuals, 26 of whom had sinus node dysfunction, and a family of 44 individuals, 13 of whom had the disease. Many of the affected individuals carried the same gene variant, and many experienced variable heart rate and bradycardia (dangerously low heart rate).
The investigators found that variants in a gene called ankyrin 2, or ANK2, resulted in dysfunction in the protein ankyrin-B in the members of these two different families, said the study's senior author Peter Mohler, Ph.D., associate professor of internal medicine in the University of Iowa Carver College of Medicine.
"While a small number of the patients displayed heart disease symptoms, including ventricular arrhythmias, the prevalence of sinus node dysfunction in these patients was extremely high. In fact, most required the implantation of cardiac pacemakers," said Mohler, who also is a Pew Scholar. "We predict that there are likely additional unidentified ankyrin variants in the larger general population that predispose humans to a combination of heart disease symptoms, including sinus nod
|Contact: Becky Soglin|
University of Iowa