Many African-Americans Have a Gene that Prolongs Life after Heart Failure

Physorg.com, April 20, 2008

About 40 percent of African-Americans have a genetic variant that can protect them after heart failure and prolong their lives, according to research conducted at Washington University School of Medicine in St. Louis and collaborating institutions.

The genetic variant has an effect that resembles that of beta blockers, drugs widely prescribed for heart failure. The new study offers a reason why beta blockers don’t appear to benefit some African-Americans.

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Co-author Stephen B. Liggett, M.D., professor of medicine and physiology at the University of Maryland School of Medicine and director of its cardiopulmonary genomics program says the discovery adds to the accumulating evidence that genetic differences contribute to the way people respond to medications and should encourage the use of genetic testing in clinical trials to identify people who can benefit from therapy tailored to their genetic makeup.

About 5 million people in the United States have heart failure, and it results in about 300,000 deaths each year. Beta blockers slow heart rate and lower blood pressure to decrease the heart’s workload and prevent lethal cardiac arrhythmias.

While Caucasians with heart failure participating in clinical studies of beta blockers have shown clear benefit from the drugs, the evidence for benefit in African-Americans has been ambiguous. The current study, reported online April 20, 2008, in Nature Medicine, identified one particular race-specific gene variant that seems to account mechanistically and biologically for these indeterminate results.

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The researchers showed that African-American heart failure patients with this genetic variant have about the same survival rate even if they don’t take beta blockers as Caucasian and African-American heart failure patients who do take beta blockers.

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The human heart has two forms of GRK: GRK2 and GRK5. The researchers meticulously searched the DNA sequence of these genes in 96 people of European-American, African-American or Chinese descent to look for differences. They found most people, no matter their race, had exactly the same DNA sequence in GRK2 or GRK5. But there was one common variation in the DNA sequence, a variation called GRK5-Leu41, the variant that more than 40 percent of African-Americans have.

To determine the effect of the GRK5-Leu41 variant, 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,” Dorn says. “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.”

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