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Genetic Variant in Blacks Mimics Heart Failure Drug

Beta blockers are an important part of the drug therapy prescribed for patients experiencing heart failure and have been proven, in many cases, to prolong the life of the heart patient.  These drugs work by suppressing the action of the hormone adrenaline, thereby slowing the heart rate and lowering blood pressure to minimize the workload that the already-weakened heart must do.  Beta blockers help prevent cardiac arrhythmias, which can be fatal.

In spite of the highly beneficial effects of beta blockers, one puzzling aspect of their use was the basis for a study conducted by a research team at St. Louis’s Washington University School of Medicine.  Seems beta blockers are a highly beneficial treatment when taken by Caucasians and many African Americans but other African Americans appear to gain no benefit at all.

The research team has found that a genetic variant, GRK5-Leu41, was found in the gene codes of about 40% of the African-American population.  This gene variant works to the benefit of the heart the same way beta blockers do.

Controversy has surrounded the efficacy of using beta blockers on African American heart failure patients because there has been little agreement as to whether they actually provided any real benefit or not.  Now it seems that beta blockers work just fine in the African American population that does not carry the GRK5-Leu41 variant but has no effect on those who do.  Researchers see the presence of this genetic variant another step toward more effective means of individualized treatment measures.

The researchers analyzed DNA sequencing to find the prevalence of two forms of genetic variant known to be associated with the heart.  These two forms, GRK2 and GRK5, were found in the genetic codes of 96 people of African-American, Chinese, and European-American descent.  The GRK5 variant appeared in some, but not all, African Americans (40%).

The research team then monitored 375 African-American heart failure patients for survival or heart transplant times.  They compared study participants who did carry the GRK5-Leu41 variant against those who did not.

It was found that the participants not taking beta blockers but who did have the genetic variant survived almost twice as long as participants with the more common GRK5 gene who were not taking beta blockers.  Participants without the variant but who took beta blockers had survival rates similar to the participants who did have the genetic variant.  When variant-positive patients were also given beta blockers, survival rate did not improve correspondingly.

Almost 5 million Americans have heart failure and almost 300,000 people die from it every year.  Beta blockers serve as energy regulators for the sudden bursts of energy that adrenaline can trigger.  By keeping the adrenaline rush in check, life-threatening heart arrhythmias can sometimes be avoided.

The full story on this study is published online in the April 20 issue of Nature Medicine.  The National Heart, Lung, and Blood Institute provided funding.

Source: Washington University School of Medicine

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