October 4, 1995
Media Contact: Michael Purdy
Phone: (410) 955-8725

"...We are clearly making headway in dissecting the complex genetic factors that can contribute to the development of asthma."

A gene that can cause the lungs to become inflamed and constricted is located on the same region of a chromosome where researchers previously located another frequent contributor to asthma--a gene that controls levels of a special immune antibody, IgE, which is associated with allergic reactions.

The finding marks the spot as a potential treasure trove of insights into the genetic causes of asthma. Further study may yield better methods for measuring the risk of developing asthma and point out new possibilities for treating asthma, according to Roy Levitt, M.D., a Hopkins professor of anesthesia and critical care medicine, and author of a new paper in the October 5 New England Journal of Medicine.

"There's still a long way to go before we can develop these clinical applications," says Levitt. "But this result is a very important first step; it's told us where to look to identify the genes that lead to the development of asthma."

A person's genetic makeup cannot by itself cause asthma or allergies, Levitt notes. Frequent exposure to substances like mold, pollen, or dust mites are needed to provoke the asthmatic or allergic reactions. A genetic predisposition to the reactions is also essential, though, and treating asthma may be easier to do by blocking these genetic contributors, Levitt speculates.

Using clinical tests and DNA samples, Hopkins researchers, together with colleagues at the University of Maryland and in the Netherlands, studied the inheritance of two contributors to asthma in 84 Dutch families: high IgE levels, which are linked to allergies; and bronchial hyperresponsiveness, which is associated with inflammation in the lungs and may result from allergic reactions. Their work was supported by the National Institutes of Health, the Dutch Asthma Funds, and the American Lung Association.

The researchers found that the characteristics were frequently inherited together; parents who had both traits tended to pass both traits to their children. This statistical link increases the likelihood that both genes for the traits may be located on the same chromosome.

"Our research team and others had previously shown that a gene that affects IgE levels is located on chromosome 5," Levitt notes.

To test whether bronchial hyperresponsiveness is located on the same chromosome, Levitt and his colleagues looked at commonly recognized markers on the chromosomes. By matching the inheritance of these markers with the inheritance of bronchial hyperresponsiveness, they provided evidence that the gene is on chromosome 5.

If a single gene on chromosome 5 affects both IgE levels and bronchial responsiveness, then it must be a powerful gene. If two genes are involved, the details of their relationship could help scientists learn more about the confusing relationship between allergy, bronchial hyperresponsiveness and asthma.

"We don't have the whole picture here," he says. "But we are clearly making headway in dissecting the complex genetic factors that can contribute to the development of asthma."

Lead author on the new paper was Dirkje Postma, M.D., of University Hospital in Groningen, the Netherlands; other authors were Kenneth Holroyd, Jenfiang Xu and Deborah Meyers, of Hopkins; Pamela Amelung and Eugene Bleecker of the University of Maryland; and Caroline Panhuysen of the Asthma Center in Beatrixoord in the Netherlands.

-- JHMI --
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