R&D News: Study connects gene variant to response to asthma drugs

The study analyzed data from over 1,000 people enrolled in five separate clinical trials that studied different steroid treatments for asthma.

Susan Shurin, acting director of the NHLBI, said: “This finding helps to explain the genetic basis for the long-standing observation that some people do not respond well to what is a common asthma treatment.

“The study illustrates the importance of research examining the relationship between genetic makeup and response to therapy for asthma, and underscores the need for personalized treatment for those who have it.”

The study first conducted a genome-wide scan of the DNA of children enrolled in the Childhood Asthma Management Program and of their parents. The genomic scan uncovered a variant in a gene called GLCCI1 that appeared to be 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 studies were white; the results may not be applicable to persons of other ethnicities.

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 regular GLCCI1 gene. Those who responded poorly had an average of one-third the level of lung improvement following inhaler treatment as did people with two regular copies of the gene.

About 1 in 6 study participants had two copies of the GLCCI1 variant, which is thought to work in conjunction with other genetic and environmental factors to affect response to ICS.

The study was also funded by the National Human Genome Research Institute and the NIH Pharmacogenomics Research Network.

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