Skip to Content

Gene Variant Could Explain Why Asthma Treatment Often Fails

The discovery could help doctors treat the 40 percent of patients who don’t respond well to inhalers.
September 26, 2011

A new study has revealed a genetic variant among asthma patients who don’t respond well to steroid inhalers, the main treatment for the disease. The discovery could lead to a DNA test that could identify such patients early on, allowing doctors to prescribe alternative treatments instead.

As many as 40 percent of asthma patients don’t respond well to steroid inhalers. Prior to the new study, published today in the New England Journal of Medicine, researchers had been unsuccessful in their attempts to identify specific genetic factors associated with such patients’ response to the relevant class of steroid hormones, called glucocorticoids.

But now, for the first time, researchers have shown a link between a gene and decreased inhaler response. The researchers found that patients with the mutation were about 2.5 times more likely to respond poorly to inhaled glucocorticoids. Cell-culture studies showed that the mutation decreased expression of a gene found in lung and immune cells that contributes to asthma symptoms.

It’s unlikely that this mutation is the sole cause of impaired asthma drug response, but the finding renews hope that clinicians can use genetics to individualize treatment plans for asthma patients. “As we identify more of these genes, and this isn’t far off, we’ll be better able to tailor asthma treatments to patients,” says study coauthor Scott Weiss, a researcher at the Channing Laboratory, a research division of Brigham and Women’s Hospital and Harvard Medical School.

Personalized medicine has always been a goal of human genetics research. When the human genome was sequenced 11 years ago, many people assumed DNA-based drug response tests were right around the corner. But by and large, this hasn’t been the case. Genomewide analyses haven’t turned up as many candidate genes as expected, and results that seemed promising have proved difficult to replicate in follow-up studies.

Studying the genetics of asthma has been particularly challenging because the symptoms vary so much from patient to patient. “It’s probably not one disease, but several disease subtypes that look very much alike,” says Michael Kabesch, an asthma genetics researcher at the Hannover Medical School in Germany.

For the new study, the researchers took advantage of a large clinical trial conducted by the National Institutes of Health that carefully monitored children’s response to asthma treatments over five years. After they linked the genetic variant to reduced glucocorticoid response in those patients, the researchers replicated the findings in patients from three other clinical trials. Combined with the cell-culture work, this enabled the researchers to tie the mutation to asthma drug response.

Weiss and his colleagues suspect that whole-genome sequencing, which is just now becoming more affordable, will help identify other genetic variants involved with glucocorticoid response. They’re also conducting pharmacology experiments on cells from patients with the mutation. “We still have to figure out exactly what this gene does,” says Kelan Tantisira, a pulmonologist at the Channing Laboratory who coauthored the study. “Then we can work toward building these predictive tests.”

Keep Reading

Most Popular

The miracle molecule that could treat brain injuries and boost your fading memory

Discovered more than a decade ago, a remarkable compound shows promise in treating everything from Alzheimer’s to brain injuries—and it just might improve your cognitive abilities.

wet market selling fish
wet market selling fish

This scientist now believes covid started in Wuhan’s wet market. Here’s why.

How a veteran virologist found fresh evidence to back up the theory that covid jumped from animals to humans in a notorious Chinese market—rather than emerged from a lab leak.

Conceptual illustration showing a file folder with the China flag and various papers flying out of it
Conceptual illustration showing a file folder with the China flag and various papers flying out of it

The US crackdown on Chinese economic espionage is a mess. We have the data to show it.

The US government’s China Initiative sought to protect national security. In the most comprehensive analysis of cases to date, MIT Technology Review reveals how far it has strayed from its goals.

conceptual illustration showing various women's faces being scanned
conceptual illustration showing various women's faces being scanned

A horrifying new AI app swaps women into porn videos with a click

Deepfake researchers have long feared the day this would arrive.

Stay connected

Illustration by Rose WongIllustration by Rose Wong

Get the latest updates from
MIT Technology Review

Discover special offers, top stories, upcoming events, and more.

Thank you for submitting your email!

Explore more newsletters

It looks like something went wrong.

We’re having trouble saving your preferences. Try refreshing this page and updating them one more time. If you continue to get this message, reach out to us at customer-service@technologyreview.com with a list of newsletters you’d like to receive.