UC Researchers Discover New Gene Defect for Heart Failure
Cincinnati--Researchers from the University of Cincinnati (UC) College
of Medicine have discovered a gene defect associated with a rapidly
progressing form of congestive heart failure that leads to death or the
need for cardiac transplantation. The results of the study, which was
sponsored by the National Institutes of Health, are published in
todayís issue of the Journal of Clinical Investigation.
Led by Stephen B. Liggett, MD, professor of medicine, the team found
that a genetic variation in the heart receptor, the beta-2 adrenergic
receptor, leads to rapid loss of the pumping function of the heart. The
genetic variation itself does not cause heart failure, but it adversely
modifies the course of the disease.
Heart failure affects 4.8 million individuals in the US and has a
five-year mortality of approximately 50 percent. Common causes of heart
failure include heart attacks, high blood pressure, viral infections,
and a dilated idiopathic form, the cause of which is not understood.
Regardless of the cause, physicians have been puzzled as to why some
patients only experience a slow loss of heart function and have an
overall good prognosis for long-term survival while others progress
from early symptoms to death within months to a few years.
The study examined the relationship between genetic mutations of the
beta-2 receptor and the progression of heart failure in 259 patients.
It found that those patients with the mutation called "Ile164" were
about five times more likely to die or require a heart transplant
compared to those patients without the mutation. After one year, 58
percent of patients with Ile164 either died or received a transplant
compared to only 24 percent of patients without the mutation.
"Our study showed a significant difference between patients with Ile164
and those without," says Liggett. "Therefore, if a patient has Ile164,
it may be an indication for early aggressive treatment even if the
current symptoms are mild. This treatment could include consideration
for early transplantation. Such early transplantation may be
problematic since there is a nationwide shortage of donor hearts
available for transplantation."
Liggett emphasizes that tests to determine if a patient has the gene
defect are only available for research use. Further studies with larger
populations will be necessary to understand how doctors can use the
results to treat their patients with heart failure.
The UC research team consisted of Liggett, Lynne Wagoner, MD, assistant
professor of cardiology, Laura Craft, PhD, research nurse in
cardiology, Richard Hornung, PhD, biostatistician with UCís Institute
for Health Policy and Health Science Research, Brian Hoit, MD,
professor of cardiology, and Richard Walsh, MD, professor of cardiology
and director of the Department of Cardiology, along with Tina McIntosh
with Molecular Tool, Inc. in Baltimore.