Navigation Links
Rare genetic variations may account for severe reaction to LABA drugs in some people
Date:1/27/2014

Winston-Salem, N.C. Jan. 27, 2014 More than 25 million people in the United States have asthma, a chronic lung disease that inflames and narrows the airways causing recurring periods of wheezing, chest tightness, shortness of breath and coughing.

Although several types of drugs are available to treat asthma, long-acting beta agonists (LABAs) are among the most commonly used and work well for most people. However, for a small subgroup of people with asthma, LABAs can cause severe, life-threatening side effects and carry a boxed safety warning from the U.S. Food and Drug Administration. The dilemma for doctors and researchers has been in determining who is at risk of a severe reaction to the drug so that alternative medications can be prescribed.

"This severe reaction only occurs in a very small percentage of people who have asthma, and we don't know what makes these people different from those who do well on this therapy," said Eugene Bleecker, M.D., director of the Center for Genomics and Personalized Medicine Research at Wake Forest Baptist Medical Center and senior author of the study, which is published in the Jan. 27 issue of Lancet Respiratory Medicine.

"We hypothesized that rare gene variants would account for uncommon and severe adverse responses to long-acting beta agonists. Because these variants occur less frequently, they have the potential to have a stronger influence on drug response." In the National Institutes of Health-funded study, researchers at Wake Forest Baptist identified and evaluated six rare gene variants within the beta2-adrenergic receptor gene, the gene that may influence the response to beta agonist drugs. These rare variants were found through the sequencing of DNA from blood samples of 191 non-Hispanic white, 197 African-American and 73 Puerto Rican asthma patients. The researchers found that African-American asthma patients had five rare variants, a far greater number compared to non-Hispanic white patients who only had one variant. The Puerto Rican patients had one variant, which had previously only been identified in African-Americans.

"Looking at different ethnic groups provides an opportunity to study rare variants that come with different ethnic ancestries. In general, older ancestral populations, such as Africans, have a higher frequency of rare genetic variants that could account for differences in responses to LABAs," said Victor Ortega, M.D., a pulmonary disease specialist at Wake Forest Baptist and first author of the study.

The researchers then evaluated 1,209 asthma patients to determine the impact of these variants on the risk of hospital admission for a severe asthma episode in the past year. They found that these rare variants significantly increased the risk for a hospital admission in asthma patients treated with a long-acting beta agonist. This association was not observed in those who were not treated with the drugs. Further analysis was conducted on two variants for effects on additional health-care related outcomes. The research team found that these variants significantly increased urgent outpatient visits and treatment with oral or injectable steroids because of increased asthma symptoms in patients treated with a long-acting beta agonist.

Finally, the team looked at data on asthma symptoms and found non-Hispanic whites who had a rare variant were more than twice as likely to have uncontrolled symptoms during LABA therapy. The finding was replicated in a separate group of 516 non-Hispanic whites who were treated with LABAs at 12- and 24-month follow-up visits.

Non-Hispanic whites from both the primary and replication groups with this rare variant were more than twice as likely to experience uncontrolled, persistent symptoms during treatment with a long-acting beta agonist.

The research team concluded that screening for these rare variants is not recommended at this time until further research can be conducted to validate the group's findings. However, genetic testing may be helpful for severe asthmatics that are being treated with multiple therapies, including high-dose inhaled steroid and long-acting beta agonists, and are still uncontrolled and very symptomatic, according to Bleecker and Ortega.

With additional research, there is the potential to identify genetic biomarkers that could predict the best treatment option for people with asthma, a goal of personalized medicine, the authors said.


'/>"/>

Contact: Marguerite Beck
marbeck@wakehealth.edu
336-716-2415
Wake Forest Baptist Medical Center
Source:Eurekalert

Related medicine news :

1. IntegraGen launches ARISk test, a genetic screening tool for autism in high-risk children
2. 2 genetic deletions in human genome linked to the development of aggressive prostate cancer
3. Head, Body Lice Are Genetically Very Similar
4. Certain Genetic Regions May Be Tied to Osteoporosis
5. Study of half siblings provides genetic clues to autism
6. Genetic variants, tobacco exposure and lung cancer risk
7. Research Gets Closer to Genetic Roots of Glaucoma
8. Moffitt researcher awarded GE grant to develop tool to detect breast cancer metastasis genetic risks
9. Genetically modified T cell therapy shown to be safe, lasting in decade-long study of HIV patients
10. Some women may be genetically predisposed to smoking-related hot flashes
11. Genetic abnormalities in benign or malignant tissues predict relapse of prostate cancer
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/5/2016)... ... May 05, 2016 , ... Tim ... program serving families of greater Dubuque, IA. The current campaign fundraises for Veteran’s ... discharged veterans. Donations to Veteran’s Freedom Center may now be made here: ...
(Date:5/5/2016)... ... 05, 2016 , ... Dr. Benjamin Stong of Kalos Facial Plastic Surgery, LLC ... Stong is double board certified and the only facial plastic surgeon in Atlanta to ... Non-surgical therapies such as stem cells can be used to provide stabilization to hair ...
(Date:5/5/2016)... , ... (PRWEB) May 05, 2016 , ... Talent ... acquisition startup, HireNurses, on the eve of National Nurses Week (May 6-12). ... and healthcare employers. With their enrollment into the Talent Tech Lab Virtual Incubation program, ...
(Date:5/5/2016)... ... May 05, 2016 , ... VisualDx ... Android devices. VisualDx is the first point of care diagnostic support system ... medicine. The system speeds diagnosis, therapy decisions and patient education for emergency ...
(Date:5/5/2016)... ... May 05, 2016 , ... ACLS ... to announce its new referral program, giving participants incentive for spreading the word ... community, and we know many professionals share resources with their friends and colleagues,” ...
Breaking Medicine News(10 mins):
(Date:5/3/2016)... PUNE, India , May 4, 2016 /PRNewswire/ ... report spreads across 154 pages, profiling 09 key ... It is a professional and in-depth study on ... providing a basic overview of the industry including ... Insulin Needles market analysis is provided for the ...
(Date:5/3/2016)... 3, 2016  Axiogenesis has acquired a major investment from Sino-German High-Tech Fund to further expand product development, strengthen ... http://photos.prnewswire.com/prnh/20160503/362921 ... ... ... ...
(Date:5/3/2016)... , May 3, 2016   BIOTRONIK , ... today announced Food and Drug Administration (FDA) approval ... that provides heart failure patients with access to ... also have remote monitoring with daily automatic transmission ... heart rate in response to physiological demands. ...
Breaking Medicine Technology: