Nature Medicine paper suggests that this particular version of GRK5 is protective, and only patients without it benefit from beta blockers.
About 40% of African-Americans have a genetic variant in GRK5 that can protect them after heart failure and prolong their lives, according to researchers. GRK5 codes for the enzyme GRK5, which depresses the response to adrenaline and similar hormonal substances.
The human heart has two forms of GRK: GRK2 and GRK5. The researchers searched the DNA sequence of these genes in 96 people of European-American, African-American, or Chinese descent.
They found most people, no matter their race, had exactly the same DNA sequence in GRK2 and GRK5. There was one, however, one common variation called GRK5-Leu41 in the DNA sequence of more than 40% of African-Americans.
To determine the effect of the variant in GRK5, the team studied the course of progression of heart failure in 375 African-American patients. They looked for survival time or time to heart transplant, comparing people with the variant to those without. Some of these patients were taking beta blockers and some were not.
In patients who did not take beta blockers, the researchers found that those with the variant lived almost twice as long as those with the more common version of the GRK5 gene. Beta blockers prolonged life to the same degree as the protective GRK5 variant but did not further increase the already improved survival of those with the variant.
“These results offer an explanation for the confusion that has occurred in this area since clinical trials of beta blockers began,” 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. “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.”
The investigators involved in the research were from Washington University, the University of Cincinnati, University of Michigan, Thomas Jefferson University, and University of Missouri. The study was published online on April 20 in Nature Medicine.