Gene Mutation in African-Americans Mimics Beta-Blocker Drugs

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.