Gene could explain why treatments fail some with asthma

Reuters News
Posted: Sep 26, 2011 7:09 AM
Gene could explain why treatments fail some with asthma

By Julie Steenhuysen

CHICAGO (Reuters) - Genetic differences could explain why some 40 percent of people with asthma do not respond to inhaled steroids used to achieve long-term asthma control.

U.S. researchers have found that asthma patients who inherited two copies of a specific gene variant were far less likely to respond to steroid inhalers than people with two copies of the more common version of the gene.

"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," said Dr. Susan Shurin, acting director of the National Heart Lung and Blood Institute, which sponsored the study released online on Monday in the New England Journal of Medicine.

The findings point the way to more personalized treatments for asthma, an inflammatory disease that affects more than 22 million Americans and some 300 million people worldwide.

Inhaled steroids work by reducing swelling of the airways.

"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," said Shurin, whose agency is part of the National Institutes of Health.

For the study, researchers from Brigham and Women's Hospital and Harvard Medical School -- both in Boston -- analyzed the genetic information from more than 1,000 people enrolled in clinical trials evaluating different asthma treatments.

The researchers used a family based model in which they studied the genetic makeup of children with asthma and their parents to identify genes that might play a role in response to inhaled steroids, such as AstraZeneca's budesonide sold under the Pulmicort brand and Glaxosmithkline's fluticasone or Flovent, a key ingredient in its Advair asthma treatment.

The team, led by Dr. Kelan Tantisira, found that people who inherited two copies of a genetic variant to the GLCCI1 gene were less likely to respond to treatment.

In the poor responders, treatment with an inhaler produced just one third of the level of lung improvement as that seen in people with two regular copies of the gene.

NEJM Editor-in-Chief Dr. Jeffrey Drazen said in an editorial the study brings researchers closer to being able to identify which patients are most likely to respond to treatment from inhaled steroids, which are used by millions of people.

But much work still needs to be done to understand how genetic differences affect asthma treatment, Drazen said.

"Although these research results are a step forward, they are not the end of the road," Drazen wrote.

He said clinical trials will need to be done to see if understanding a person's genetic response to drugs helps improve treatment results.

The findings were presented on Monday at the European Respiratory Society Congress in Amsterdam.