Animal Study Finds 291 Asthma Genes

Findings identify multiple pathways to illness

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MONDAY, June 16, 2003 (HealthDayNews) -- Scientists have now identified 291 genes that are associated with asthma, compared to only the dozen or so that had been previously linked to the illness.

The finding, says Marc Rothenberg, study author and director of Allergy and Immunology at the Cincinnati Children's Hospital Medical Center, provides an opportunity to explore new ways to treat the disease.

"These 291 genes, called 'signature genes,' may serve as diagnostic markers, phenotypic predictors, or possibly as targets for drug development," Rothenberg says.

One gene, arginase, seems particularly active in asthma, and could be a focus for pharmaceutical research. Medication that altered the gene's response to asthma could reduce the scarring and inflammation that characterize the illness, Rothenberg says.

A report on the research appears in the July issue of the Journal of Clinical Investigation.

Another asthma expert urges caution in assessing the results of the study.

"This is a nice piece of science, but it is a huge jump to go from an observation to a viable drug treatment," says Charles Irvin, director of the Vermont Lung Center and a professor of medicine at the College of Medicine at the University of Vermont in Burlington.

"Asthma is an incredibly complex disorder," he adds, and affects people in many different ways. So even if a treatment that altered the arginase gene was developed, it would only be effective in a very small percentage of patients, perhaps 10 percent.

In the study, Rothenberg and his colleagues took lung tissue from mice in which asthma had been induced by exposure to different allergens. Using new DNA microarray technology, called gene chips, they found that 291 genes -- or 6.5 percent of the mouse genome -- were altered in an asthmatic lung.

Particularly activated was arginase, which is associated with asthma symptoms, Rothenberg says: "The asthma will induce arginase activation, which [through processing an amino acid called arginine] will affect production of polyamines; collagen, which is involved in fibrosis and scarring; and nitric oxide, which is involved in inflammation and airflow regulation."

Rothenberg reports that before this, it was thought that another gene, nitric oxide synthase (NOS), was responsible for the activations producing inflammation and scarring.

"Our results challenge the conventional view that arginine is primarily metabolized by NOS in asthmatic responses; rather, we propose that significant metabolism occurs by arginase, and that this process has important ramifications on the manifestations of the disease," the study states.

More than 17 million American have asthma, including 4.8 million children, according to the National Institute of Allergy and Infectious Diseases, and more than 5,000 people die from asthma each year in the United States. Although asthma deaths are infrequent, they have more than doubled in the last two decades, from 8.2 per 100,000 people from 1975 to 1979 to 17.9 per 100,000 from 1993 to 1995.

More information

An overview of asthma and its effects can be found at the National Library of Science. For tips on controlling allergens in your home, go to the American Lung Association.

SOURCES: Charles Irvin, Ph.D., director, Vermont Lung Center, and professor, medicine, University of Vermont, Burlington; Marc Rothenberg, M.D., Ph.D., director, Allergy and Immunology, Cincinnati Children's Hospital Medical Center; July 2003 Journal of Clinical Investigation
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