New research revealed that a gene variant carried by about
40 percent of African-Americans protects them after heart failure as much as
widely used beta-blocker drugs do.
The findings could explain why clinical trials of the drugs
have shown little benefit to African-American patients.
“To our knowledge, this is the first case where a genetic
variant mimics the activity of a drug used to treat a disease,” said Dr.
Stephen B. Liggett, a professor of medicine and physiology at the University of Maryland, and co-author of the study,
the Washington Post reports.
Heart failure, a condition caused by a number of diseases
including diabetes and hypertension, results in inefficient blood pumping from
the heart to the rest of the body. During the crisis, the body releases
adrenaline to keep the organ pumping. Too much adrenaline overworks the heart,
and eventually the organ gives out. Beta-blockers are specially designed to block
adrenaline receptors and slow the heart rate.
Researchers at the University of Maryland, Baltimore,
and Washington University
in St. Louis, Missouri analyzed GRK5, one of the receptor proteins
in the heart that responds to adrenaline. After sequencing DNA from 96
heart-failure patients, the team found that 40 percent of African Americans in
the study had a mutation in GRK5. Only 2 to 3 percent of participants of
European or Chinese descent had this variant, called Leu41.
People with the variant gene could be said to have a natural beta-blocker. 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.
“That doesn't mean African-Americans
with heart failure need to be tested for the genetic variant to decide whether
to take beta blockers. Under the supervision of a cardiologist, beta blockers
have very low risk but huge benefits, and I am comfortable prescribing them to
any heart failure patients who do not have a specific contraindication to the
drug,” says senior author Gerald W. Dorn II, M.D., professor of medicine,
associate chairman for translational research and director of the Center for
Pharmacogenomics at Washington
University.
He further adds: “These results offer an explanation for the confusion that
has occurred in this area since clinical trials of beta blockers began. Our
study demonstrates a mechanism that should lay to rest the question about
whether beta blockers are effective in African-Americans -- they absolutely are
in those who don't have this genetic variant.”
About 5 million people in the United States have heart failure,
which results in about 300,000 deaths each year.
The study, funded by the National Heart, Lung, and Blood Institute, appeared
online in the April 20 issue of Nature Medicine.
