Gene variant associated with reduced response to asthma inhalers

A large number of the world’s 300 million people with asthma -- as many as 40% -- don’t respond to the inhalers their doctors prescribe to improve lung function. But doctors don’t know how to predict which patients will benefit from glucocorticoid therapy (steroid inhalers) and which ones won’t.

But researchers at the Harvard Medical School have now located a genetic variation that may some day help physicians figure it out.

The team’s results, published Monday in the New England Journal of Medicine, used a genome-wide analysis of 118 trios (consisting of a child and his or her parents) to identify a variant in a gene called glucocorticoid-induced transcript 1 gene, or GLCCI1. As its name suggests, GLCCI1 is associated with response to the drugs.

People who have two copies of the variant (and of another variant that is perfectly correlated with it) had an average increase in exhalation volume of about 3.2% when they used a glucocorticoid inhaler. People with no copies of the variant had about a 9.4% improvement from the treatment.

About 16% of the population will have two copies of the variant, noted Harvard pulmonologist Jeffrey M. Drazen in an editorial accompanying the study.

Drazen called the effect of having the genetic variation “appreciable but not overwhelming” but noted that the research could be a first step toward being able to identify who will and who won’t respond to treatment.

“The next step must be to mount clinical trials in which patients are stratified according to their biologic signature to determine whether knowledge of this information leads to better clinical outcomes,” he wrote.