03:08pm Saturday 28 March 2020

Researchers find connection between gene variant and poorer response to asthma drugs

Researchers at Brigham and Women’s Hospital (BWH) found that asthmatics who have two copies of a specific gene variant only responded one-third as well to steroid inhalers as people with two copies of the normal gene. The results appear in the September 26 online edition of the New England Journal of Medicine.

Asthma is a complex inflammatory disease that affects over 22 million people in the United States and roughly 300 million people worldwide. Many factors can affect how severely the disease affects people and how well they respond to treatments. Poor response to inhaled corticosteroids (ICS) often runs in families, suggesting that genetics plays a role in how people respond to asthma treatments.

The study, lead by Kelan Tantisara, MD, MPH, a researcher in the Channing Laboratory at BWH, first conducted a genome-wide screening of the DNA of children enrolled in the Childhood Asthma Management Program (CAMP) as well as their parents. The screening uncovered that a variant in a gene called GLCCI1 was potentially associated with poor ICS response. Study researchers then verified this association in 935 additional people with asthma, both children and adults, enrolled in four independent ICS studies. Most of the participants in these groups were Caucasian, so the results may not be applicable to all demographics.

In this study, people carrying two copies of the GLCCI1 variant were more than twice as likely to respond poorly to ICS treatment as participants with two copies of the normal GLCCI1 gene. On average, the poor responders only had one-third the level of lung improvement following inhaler treatment compared to people with two regular copies of the gene.
The researchers suggest that GLCCI1 normally is stimulated by inhaled steroids to produce a protein that helps destroy the inflammatory cells that invade the lungs of asthma patients. The GLCCI1 variant may lower how much GLCCI1 protein gets produced in response to steroid treatment, which in turn reduces the lungs’ ability to kill these inflammatory cells.  

About 1 in 6 study participants had two copies of the GLCCI1 variant, which likely works in conjunction with other genetic and environmental factors to affect response to ICS. More studies will be needed to understand how GLCCI1 operates in the lungs and to explore whether it contributes to response in patients of other ethnic groups. 

The research was funded by the National Heart, Lung, and Blood Institute, part of the National Institutes of Health.

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