Genetic Differences Can Coincide with Response to Steroid-Based Asthma Treatment

treatments for asthma patients
New research from Cleveland Clinic and others

Researchers recently found a genetic variant associated with poor overall lung function also appears to coincide with poorer-than-usual response to glucocorticoid-based asthma treatment.

The work reveals biology that may also hold clues to understanding responses to other asthma therapies.

“These findings provide us with important new information that may lead to more tailored treatments for asthma patients and the ability to prevent the development of severe disease,” first author Joe Zein, a pulmonologist at the Cleveland Clinic’s Lerner Research Institute and Respiratory Institute, said in a statement.

The study appeared online recently in the Proceedings of the National Academy of Sciences. Researchers at the Cleveland Clinic and Indiana University School of Medicine tapped into genome sequence data for just under 2,000 individuals with asthma, profiled for the Severe Asthma Research Programs (SARP) sponsored by the National Heart, Lung, and Blood Institute.

“Glucocorticoids, which modulate systemic inflammatory response, are commonly prescribed to treat severe asthma. However, until now we have not understood why many patients do not benefit from them,” senior and corresponding author Nima Sharifi, a researcher and physician at the Lerner Research Institute, said in a statement.

The researchers’ focus was on one gene in particular, HSD3B1, which is a steroid hormone-related enzyme-coding gene that typically converts a compound called dehydroepiandrosterone (DHEA) from the adrenal gland to androgen hormones.

When the team genotyped HSD3B1 in 318 glucocorticoid-treated or non-glucocorticoid-treated asthma patients with available lung function measurements, it found that a missense variant that is linked to reduced conversion to androgen coincided with poorer-than-usual treatment response and reduced forced expiratory volume, a measure of lung function. 

“These data suggest that androgen depletion, whether circulating and/or at the tissue level, could contribute to the pathophysiology of severe asthma and resistance to oral [glucocorticoid] therapy,” the authors wrote.

SOURCE: Genome Web

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