Genetic variation mimics drugs frequently used to treat heart failure

London, Apr 21 : Scientists at University of Maryland School of Medicine in Baltimore and the Washington University School of Medicine in St. Louis have found that a genetic variant, GRK5, acts just like beta-blockers, a class of drugs used to treat chronic heart failure, and that it naturally protects certain people from heart failure and need for a heart transplant.

The researchers also found that the variant is commonly found in African American patients, whose in built "genetic beta blockade" actively protects them.

According to the researchers, this discovery may encourage the use of genetic testing in clinical trials for identifying those patients who can be benefited by a personalized therapy according to their personal genetic makeup.

"This is a significant development in our understanding of why some African American patients appear to not respond to beta-blockers in the same way as Caucasian patients. In this case, it seems that this genetic variation is a good thing, mimicking drugs that are frequently used to treat heart failure," Nature Medicine quoted Stephen B. Liggett, co-author of the study, as saying.

Few patients are benefited by beta-blockers, which allow the heart to get some relief from the overactive pumping due to heart failure, by developing a more normal cellular structure, and shrinking in size. This happens as beta-blockers block or tone down the fight or flight response.

Researchers took genetic profiles of more than 2,000 volunteers in Cincinnati, Kansas City and Atlanta, including Americans of European descent and African Americans. Few volunteers had heart failure, others had ischemia; healthy volunteers made up a third group.

For better understanding of the genetic variation, they created cell lines and developed genetically altered mice and found that the genetic variant worked identically to beta-blocker drugs, reducing the impact of adrenalin that forces the heart to work harder.

In an experimental model, it was the variant that protected the mice from developing heart failure after exposure to a substance similar to adrenaline.

After this finding a prospective study was launched involving 375 African Americans with heart failure at the University of Cincinnati. While some were on beta-blockers and some were not. The participants were followed for an average of of two-and-a-half years and it was found that those with the variant who had heart failure were just as protected as those without the variant who were on beta-blockers.

"For several years, a controversy has existed in the cardiovascular field because of conflicting reports about whether beta-blockers helped African-American patients. By mimicking the effect of beta-blockers, the genetic variant makes it appear as if beta blockers aren't effective in these patients," said co-author Gerald W. Dorn II.

The study is available in the online version of Nature Medicine.

ANI