Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Genetic variants associated with bronchodilator responsiveness

25.10.2013
How patients with COPD respond to their meds may be influenced by their DNA

A new study from Brigham and Women's Hospital (BWH) reveals several new gene variants that are associated with how people living with chronic obstructive pulmonary disease (COPD) respond to inhaled bronchodilators.

COPD is a progressive breathing disorder that limits airflow in the lungs. Bronchodilators are medicines used to alleviate respiratory disorder symptoms.

The abstract for this meta-analysis study will be presented at the American Society of Human Genetics 2013 meeting, Oct. 22 to 26 in Boston.

One of the research goals was to identify single nucleotide polymorphisms (SNPs) associated with bronchodilator responsiveness (BDR).

"Identifying single nucleotide polymorphisms associated with bronchodilator responsiveness may reveal genetic pathways associated with the pathogenesis of COPD and may identify novel treatment methods," said Megan Hardin, MD, BWH Channing Division of Network Medicine, lead study author.

The researchers used statistical methods to combine results from 5,789 Caucasian patients with moderate to severe COPD from four individual studies. The genotypes of over 700 African Americans with COPD were also analyzed.

Most (4,561) of the patients in the four cohorts studied had over 10 pack-years of smoking. The group whose members had greater than 5 pack-years of smoking totaled 364, and the cohort with greater than two and one-half years totaled 864.

All patients were genotyped, and their lung function was tested by spirometry before and after they used the bronchodilator medication albuterol, which relaxes muscles in the airways and increases air flow to the lungs. Spirometry measures the volume and flow of air that is exhaled.

The researchers investigated over 6.3 million unique SNPs from the patients' genotypes. They discovered four novel variants that rarely occur in the general population.

According to Hardin, there may be multiple genetic determinants that likely influence bronchodilator responsiveness. The researchers caution that more extensive functional analysis of the SNPs will be required.

"As we continue to analyze the data, we expect to identify other important SNPs," said Craig P. Hersh, MD, BWH Channing Division of Network Medicine, senior study author.

Each patient's bronchodilator responsiveness (BDR) was determined by three measures: absolute change in the volume of air exhaled during a forced breath in one second (FEV1) (BDRABS); change as percentage of predicted FEV1 (BDRPRED); and change as percentage of baseline FEV1 (BDRBASE).

The researchers reported that the top SNPs thus far have been associated with each BDR outcome, but emphasized that additional analysis may reveal other SNPs with equally or greater influence on COPD patients' response.

The meta-analysis revealed the top SNPs for each BDR outcome:

SNPs in the:

HS6ST3 gene were associated with BDRBASE
XKR4 gene were associated with BDRPRED and BDRBASE
CUBN gene were associated with BDRABS and BDRPRED
Among African American participants, SNPs in the CDH13 gene were significantly associated with BDRABS.

The cohorts included in the meta-analysis were: ECLIPSE (1,764 patients) and COPDGene (2,797 patients), all of whom had over 10 pack-years of cigarette smoking; NETT (364 patients) with over five pack-years smoking; and GenKOLs (864 patients with over 2.5 pack-years of smoking).

This research was supported by the National Institutes of Health (R01HL094635, R01NR013377, R01HL089856, R01HL089897, P01HL083069). COPDGene was additionally supported by the COPD Foundation. ECLIPSE and GenKOLs were supported by GlaxoSmithKline.

Brigham and Women's Hospital (BWH) is a 793-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare. BWH has more than 3.5 million annual patient visits, is the largest birthing center in New England and employs nearly 15,000 people. The Brigham's medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in patient care, quality improvement and patient safety initiatives, and its dedication to research, innovation, community engagement and educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Biomedical Research Institute (BRI), BWH is an international leader in basic, clinical and translational research on human diseases, more than 1,000 physician-investigators and renowned biomedical scientists and faculty supported by nearly $650 million in funding. For the last 25 years, BWH ranked second in research funding from the National Institutes of Health (NIH) among independent hospitals. BWH continually pushes the boundaries of medicine, including building on its legacy in transplantation by performing a partial face transplant in 2009 and the nation's first full face transplant in 2011. BWH is also home to major landmark epidemiologic population studies, including the Nurses' and Physicians' Health Studies and the Women's Health Initiative. For more information and resources, please visit BWH's online newsroom.

Marjorie Montemayor-Quellenberg | EurekAlert!
Further information:
http://www.brighamandwomens.org/

More articles from Studies and Analyses:

nachricht Innovative genetic tests for children with developmental disorders and epilepsy
11.07.2018 | Christian-Albrechts-Universität zu Kiel

nachricht Oxygen loss in the coastal Baltic Sea is “unprecedentedly severe”
05.07.2018 | European Geosciences Union

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Machine-learning predicted a superhard and high-energy-density tungsten nitride

18.07.2018 | Materials Sciences

NYSCF researchers develop novel bioengineering technique for personalized bone grafts

18.07.2018 | Life Sciences

Why might reading make myopic?

18.07.2018 | Health and Medicine

VideoLinks
Science & Research
Overview of more VideoLinks >>>