MONDAY, April 21 (HealthDay News) -- Researchers have discovered
a gene variant carried by about 40 percent of blacks that protects
them after heart failure as much as widely used beta blocker drugs
do.
The finding explains the puzzling results reported in trials of
beta blocker therapy in black people, said Dr. Stephen B. Liggett,
a professor of medicine and physiology at the University of
Maryland, and co-author of a report in the April 20 online issue of
Nature Medicine.
"To our knowledge, this is the first case where a genetic
variant mimics the activity of a drug used to treat a disease,"
Liggett said.
But Liggett predicted "further surprises" along the same lines
as research on human genetic variations continues.
The finding won't have an immediate effect on treatment of heart
failure, the progressive loss of ability to pump blood that affects
an estimated 5 million Americans, said study co-author Dr. Gerald
W. Dorn II, director of the Center for Pharmacogenomics at
Washington University in St. Louis. Doctors can continue to
prescribe beta blockers for people with heart failure, black or
white, since the drugs have little risk, he said.
But there should be an effect on future medical practice, Dorn
said. "One idea in the future of drug discovery is that we will not
only need to tailor therapy for individual genetic makeup but also
take genetic makeup into consideration in drug testing," he
explained.
About 2 percent to 3 percent of white Americans in the total
group of 2,000 who were tested carried the gene variant, he
said.
The research finding was made possible by the Human Genome
Project, which laid out all the more than 20,000 genes that act in
humans. The researchers zeroed in on the gene pathway responsible
for the activity of adrenaline, a hormone that increases cardiac
output. In heart failure, the adrenal glands produce more and more
adrenaline to increase blood flow. Overproduction of adrenaline
causes the heart to weaken faster. Beta blockers ease the pressure
on the heart by blocking adrenaline receptors in heart muscle.
The researchers looked at two genes in the adrenaline pathway,
GRK2 and GRK5. They found one specific variant, designated
GRK5-Leu41, that reduced the effect of adrenaline on heart cells. A
study of 375 black adults with heart failure showed that among
those not taking beta blockers, those with the GRK5-Leu41 variant
lived twice as long as those with the more common variant. The same
prolonged survival was seen in those with the normal variant who
took beta blockers. Beta blocker therapy did not increase the
survival of individuals with the helpful gene variant.
The same kind of genetic analysis will inevitably be extended to
other drugs and other diseases, Liggett said.
"Our idea is not to replace the physician's judgment, but to
give a handle on which drugs they might want to push to higher
levels and which are less likely to be helpful for specific
individuals," he said.
More information
Heart failure and its treatment are described by the
U.S. National Library of Medicine.
