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

ll lines and developed genetically altered mice to predict how the gene would function in humans. They discovered that the genetic variant acts in a way that is identical to beta-blocker drugs, reducing the impact of adrenalin that forces the heart to work harder. In an experimental model, the variant protected the mice from developing heart failure after exposure to a substance similar to adrenaline.

Armed with this information, they launched a prospective study of 375 African Americans with heart failure at the University of Cincinnati and followed them for an average of two-and-a-half years. Some were on one of the two commonly used beta-blockers in the United States (carvedilol or metoprolol); others were not on beta-blockers. While the presence of the variant did not prevent the onset of heart failure, those with the variant who had heart failure were just as protected as those without the variant who were on beta-blockers.

The researchers say this particular genetic variant occurred in about 40 percent of African Americans they studied. The variant also occurs in about two percent of Caucasians. While it is likely to be a factor in those patients as well, a much larger study would be required to verify this, because the variant is so uncommon.

For several years, a controversy has existed in the cardiovascular field because of conflicting reports about whether beta-blockers helped African-American patients, says co-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. By mimicking the effect of beta-blockers, the genetic variant makes it appear as if beta blockers arent effective in these patients.

According to Dr. Liggett, the discovery of this variant is another milestone on the road to personalized medicine. In heart failure treatment, there is still a lot of
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Contact: Bill Seiler
bseiler@umm.edu
410-484-7317
University of Maryland Medical Center
Source:Eurekalert

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