Navigation Links
Genetic variant mimics effect of heart failure medications

A genetic variation, found predominantly in African Americans, protects some people with heart failure, enabling them to live longer than expected. Thats the conclusion of a research team led by investigators at the University of Maryland School of Medicine in Baltimore and the Washington University School of Medicine in St. Louis. The researchers found that the genetic variation acts just like beta-blockers, a class of drugs used to treat chronic heart failure. Study results will be available in the online version of Nature Medicine (, on April 20, 2008.

In the study, the researchers found that African American heart failure patients with the genetic variation had a natural protection against death and the need for a heart transplant that is the same as the protection provided by beta-blocker therapy. Those patients who were given beta-blockers did not experience additional benefits from the medications because their own genetic beta blockade was already protecting them.

The researchers say their 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 personal genetic makeup. This is a significant development in our understanding of why some African American patients appear to not respond to beta-blockers in the same way as Caucasian patients, says one of the studys co-authors, 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. In this case, it seems that this genetic variation is a good thing, mimicking drugs that are frequently used 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 cell 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 one drug fits all thinking. This variant is one of what may be many genetic variants that can be used like a scorecard to guide treatment in a much more personalized way, says Dr. Liggett. He adds that the University of Maryland School of Medicine has multiple research studies underway to further identify by genetic means which patients should be treated with which drugs.


Contact: Bill Seiler
University of Maryland Medical Center

Related biology news :

1. Does the desire to consume alcohol and tobacco come from our genetic makeup?
2. Diverse genetic abnormalities lead to NF-κB activation in multiple myeloma
3. Many parents at-risk for cancer disclose genetic test results to children
4. Genetics determine optimal drug dose of common anticoagulant
5. Claims of sex-related differences in genetic association studies often not properly validated
6. American College of Medical Genetics responds to new FDA labeling decision for warfarin
7. UNC study questions FDA genetic-screening guidelines for cancer drug
8. Genome study shines light on genetic link to height
9. Selexis Announces Advanced Approach to Maximize Power of Genetic Elements for Rapid Development of High Performance Cell Lines
10. Genes, Environment and Health Initiative invests in genetic studies, environmental monitoring
11. Rutgers Genetics receives $7.8 million for autism research
Post Your Comments:
(Date:11/19/2015)... Nov. 19, 2015  Based on its in-depth analysis ... recognizes BIO-key with the 2015 Global Frost & Sullivan ... & Sullivan presents this award to the company that ... the needs of the market it serves. The award ... and expands on customer base demands, the overall impact ...
(Date:11/18/2015)... PHILADELPHIA , Nov. 18, 2015  As new ... in children, doctors and other healthcare providers face challenges ... counsel families and patients. In addition, as more children ... into a patient,s adulthood and old age. ... The Children,s Hospital of Philadelphia (CHOP) . ...
(Date:11/17/2015)... -- Paris from 17 th ... Paris from 17 th until 19 th ... has invented the first combined scanner in the world which ... surface. Until now two different scanners were required: one for ... on the same surface. This innovation is an ideal ...
Breaking Biology News(10 mins):
(Date:11/24/2015)... 2015 --> ... "Oligonucleotide Synthesis Market by Product & Services (Primer, Probe, ... DNA, RNAi), End-User (Research, Pharmaceutical & Biotech, Diagnostic Labs) ... market is expected to reach USD 1,918.6 Million by ... CAGR of 10.1% during the forecast period. ...
(Date:11/24/2015)... (PRWEB) , ... November 24, 2015 , ... The Academy ... Special Interest Group (SIG), MultiGP, also known as Multirotor Grand Prix, to represent the ... last few years. Many AMA members have embraced this type of racing and several ...
(Date:11/24/2015)... New York , November 24, 2015 ... to a recent market research report released by Transparency ... projected to expand at a CAGR of 17.5% during ... "Non-invasive Prenatal Testing Market - Global Industry Analysis, Size, ... estimates the global non-invasive prenatal testing market to reach ...
(Date:11/24/2015)... CITY , Nov. 24, 2015 /PRNewswire/ - ... "Company") announced today that the remaining 11,000 post-share ... Share Purchase Warrants (the "Series B Warrants") subject ... were exercised on November 23, 2015, which will ... Shares.  After giving effect to the issuance of ...
Breaking Biology Technology: