Genetic variants associated with bronchodilator responsiveness

October 25, 2013

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 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 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 ).

Explore further: DNA variants may influence COPD patients' response to inhaled bronchodilators

Related Stories

DNA variants may influence COPD patients' response to inhaled bronchodilators

October 25, 2013
Several novel gene variants may help explain the response of patients with chronic obstructive pulmonary disease (COPD) to inhaled bronchodilators, according to a meta-analysis reported today (Oct. 25) at the American Society ...

New class of drug shows promise for treating asthma and COPD

October 24, 2013
Scientists have developed a new drug (RPL554) that could treat obstructive airway diseases such as asthma and chronic obstructive pulmonary disease (COPD) in two ways at once, according to new research published in The Lancet ...

Race and gender influence diagnosis of COPD

May 21, 2013
African-Americans are less likely than whites and women are more likely than men to have had a prior diagnosis of chronic obstructive pulmonary disease (COPD) regardless of their current disease severity, according to a new ...

Inflammation is associated with depression in COPD patients

May 21, 2013
Depression is common in patients with chronic obstructive pulmonary disease (COPD) and has been linked with disease severity and impaired quality of life. Now, for the first time, researchers at the University of Pittsburgh ...

Genetic variant implicated in lung cancer development also linked with improved outcomes among affected patients

October 18, 2013
Lung cancer is the most common cause of cancer death in much of the industrialized world, including Japan. While cigarette smoke is most frequently the source of the disease, genetics can also play a role. Scientists have ...

Large study of COPD drug finds two types of inhalers equally safe and effective

September 9, 2013
An international study led by a Johns Hopkins pulmonary expert finds that the drug tiotropium (marketed as the Spiriva brand), can be delivered safely and effectively to people with chronic obstructive pulmonary disease (COPD) ...

Recommended for you

Scientists provide insight into genetic basis of neuropsychiatric disorders

July 21, 2017
A study by scientists at the Children's Medical Center Research Institute at UT Southwestern (CRI) is providing insight into the genetic basis of neuropsychiatric disorders. In this research, the first mouse model of a mutation ...

Scientists identify new way cells turn off genes

July 19, 2017
Cells have more than one trick up their sleeve for controlling certain genes that regulate fetal growth and development.

South Asian genomes could be boon for disease research, scientists say

July 18, 2017
The Indian subcontinent's massive population is nearing 1.5 billion according to recent accounts. But that population is far from monolithic; it's made up of nearly 5,000 well-defined sub-groups, making the region one of ...

Mutant yeast reveals details of the aberrant genomic machinery of children's high-grade gliomas

July 18, 2017
St. Jude Children's Research Hospital biologists have used engineered yeast cells to discover how a mutation that is frequently found in pediatric brain tumor high-grade glioma triggers a cascade of genomic malfunctions.

Late-breaking mutations may play an important role in autism

July 17, 2017
A study of nearly 6,000 families, combining three genetic sequencing technologies, finds that mutations that occur after conception play an important role in autism. A team led by investigators at Boston Children's Hospital ...

Newly discovered gene variants link innate immunity and Alzheimer's disease

July 17, 2017
Three new gene variants, found in a genome wide association study of Alzheimer's disease (AD), point to the brain's immune cells in the onset of the disorder. These genes encode three proteins that are found in microglia, ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.