Study Ties Genetic Anomaly to Poor Response for Asthma Treatment

By Adam Hochron
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Despite glucocorticoids (GC) being a standard treatment option for patients with severe asthma, some people do not respond. 

A recent study found a genetic anomaly could help explain why these patients do not respond as well. 

Results of the study, conducted by researchers at the Cleveland Clinic, were published in the Proceedings of the National Academy of Sciences

The researchers found that the HSD3B1 gene, and more specifically, the HSD3B1 (1245A) variant, has been connected with poor lung function and glucocorticoid treatment resistance, according to a press release from Cleveland Clinic. 

Previous studies have shown that the HSD3B1 gene converts less active androgens to more powerful androgens. 

Joe Zein, MD, lead author for the study and a pulmonologist at the Cleveland Clinic told MD /alert that while glucocorticoids have been known to cause suppression of dehydroepiandrosterone sulfate (DHEA-S), the hypothesis for the study was that low androgen levels caused by the glucocorticoid therapy could have a “detrimental” effect in asthma care. 

“Normally, without the mutation, low serum DHEA-S caused by chronic glucocorticoid therapy, result in low dihydrotestosterone (potent androgen with anti-inflammatory effect),” Zein said. “Those patients are considered to have glucocorticoid resistance because glucocorticoid therapy fails to improved lung function, which is low in those patients without the mutation.” 

The study included 318 patients who had been enrolled in the SARP III study and had both genotyping and pulmonary function testing data available. 

Of the patients involved in the SARP III trial, 60% had severe asthma, and 17% were treated with chronic oral ad or/injectable GCs. 

The authors noted in their findings that those with the variant were found to also have poorer lung function than those who did not have the anomaly. 

This is not the first time researchers at Cleveland Clinic have studied the gene. In 2013, Nima Sharifi, MD, and colleagues found that prostate cancer cells with the HSD3B1(1245C) variant are better able to survive androgen deprivation therapy, which is a popular treatment for prostate cancer, much the same way glucocorticoids are a popular option for severe asthma patients. 

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