Study links 291 genes to asthma

CINCINNATI — For years, researchers knew asthma was a complicated disease.

But now, a massive genetic analysis in mice led by experts at Cincinnati Children's Hospital Medical Center shows the breathing disorder is much more complicated than thought.

Not one, not 10 or 20, but 291 different genes are associated with asthma, according to the study, published in the July issue of the Journal of Clinical Investigation.

"We are literally defining the asthma genome, which will have tremendous long-term implications for research," said the study's senior author, Dr. Marc Rothenberg, director of allergy and immunology at Cincinnati Children's.

Dr. Marc Rothenberg of the Division of Allergy and Immunology at Cincinnati Children's Hospital, holds a gene chip used in the study that found 291 genes are associated with asthma, offering new ways to study the disease. Gannett News Service

"This is a very interesting finding, but it's still too early to say how this is going to affect people," said Jodi Giammarco, executive director of the Canada-based Childhood Asthma Foundation. "If it is this complicated, then there's a lot of work to be done to find a cure."

More than half of the 291 mouse genes reported by the study have never been linked with asthma before, which offers the medical world a bounty of new ways to study and potentially treat the disease, Rothenberg said. Already, Cincinnati Children's researchers believe one of the newly linked genes — called arginase — may play a powerful role in asthma and may serve as a new target for developing better treatments.

And with so many genes involved, experts may rethink the entire concept of asthma. Rather than one distinct disease, asthma may become an umbrella term like cancer, which actually describes hundreds of kinds of tumors.

"Two wheezing people coming into the doctor's office may look the same in lung function tests, but what's going on at the cellular level could be completely different," Rothenberg said. "One patient might respond well to prednisone. Another might respond to Singulair. Someday, we may be able to develop a genetic fingerprint of a person's asthma and be able to figure out exactly what to do for that individual."

Arginase is just one of the 291 genes identified in the Children's Hospital study, but it appears important because it was found well "upstream" in the flow of biological processes that lead to asthma.

Turning on the arginase gene — such as by exposing the lung to an allergy-causing substance — causes the body to produce argenine, an amino acid that plays multiple roles in the body including a useful role in liver function.

But in the lungs of a person with asthma, the substance breaks down into four different byproducts that can cause airway contraction, airway inflammation and excess mucus production.

"If you have asthma, you can take all the antihistamines you want, but it won't be a cure because all you're doing is blocking one of the last steps in the asthmatic reaction. To cure the disease, you have to be more upstream," Rothenberg said.

Steroids appear to have more of an upstream effect than antihistamines, but they also come with strong side effects in some people. No one knows yet what kind of side effects might occur from blocking arginase.

The advantage in this case is that more information about those potential risks can be generated much faster than in years past. The same DNA technology that helped spot arginase also can be used to see how every part of the human genome reacts when and if a drug is developed to block arginase.