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Genetic variant mimics effect of heart failure medications
Date:4/20/2008

d to treat heart failure, says Dr. Liggett.

Heart failure refers to the hearts inability to pump adequate amounts of blood through the body. Heart failure can be the result of hypertension or a heart attack. In some cases, called idiopathic cardiomyopathy, the cause is not identified. As heart failure progresses, adrenalin produces a fight or flight response to stimulate the heart into action by binding to receptors on heart cells called beta-adrenergic receptors. Over time, this attempt to enhance pumping in the diseased heart causes it to enlarge, change shape, and become even less effective as a pump.

In some patients, beta-blockers allow the heart to get some relief from the overactive pumping, develop a more normal cellular structure, and shrink in size. They do this by blocking or toning down the fight or flight response. Beta-blockers are a standard, highly effective therapy in some, but not all, patients with heart failure and ischemia, a cardiac blood flow disorder. But among African Americans, for unclear reasons, beta-blockers have had variable success.

To unravel this mystery, the researchers looked for human genetic variants in two types of genes associated with cardiac function, GRK2 and GRK5. These act as natural brakes to hold down overactive beta receptors. The researchers thought variants in these genes might modify the risk or outcome of heart failure, or alter the response to heart failure therapy. Nothing unusual came out of their search of the GRK2 gene.

However, in GRK5, they discovered a genetic variant. This was accomplished by taking genetic profiles of more than 2,000 volunteers in Cincinnati, Kansas City and Atlanta, including Americans of European descent and African Americans. Some of the volunteers had heart failure; others had ischemia; healthy volunteers made up a third group.

To deepen their understanding of the genetic variation, the researchers created ce
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Contact: Bill Seiler
bseiler@umm.edu
410-484-7317
University of Maryland Medical Center
Source:Eurekalert

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