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More News From the Genetic Frontier of Asthma

Specific gene identified as a contributor to chronic condition

THURSDAY, Jan. 10, 2002 (HealthDayNews) -- Moving one step closer to the use of genetics in treating asthma, researchers have identified another gene that plays a role in the ailment.

The gene, called T-bet, controls the production of interferon-gamma, a molecule in the family of cytokines, which act as growth factors. Interferon-gamma stimulates the T-cells that are active in the immune system.

Genetically engineered mice that lack the T-bet gene have the kind of inflammation of the airways seen in human asthma, a group at Harvard Medical School reports in tomorrow's issue of Science. In addition, tests of seven humans with asthma showed significantly reduced T-bet activity, the researchers say.

"These data suggest that T-bet might be an attractive target for the development of anti-asthmatic drugs," they write.

The discovery is part of an emerging field linking specific genes with asthma, says Dr. Lanny Rosenwasser, head of adult allergy at the National Jewish Medical and Research Center in Denver. He has identified some genes, and has done collaborative work with the Harvard group.

"This study demonstrates that one of a class of genes that control T-cell activation are involved in asthma," Rosenwasser says. "It's a good paper because it has human correlates to the animal model."

Rosenwasser ticks off the names of other molecules that have similar activity and are involved in asthma: GATA3, CMAF, NATF 1 through 4.

Half a dozen of these genes, including T-bet, look promising, Rosenwasser says, "but direct treatment is at least five years in the future." And no one gene plays a dominant role; each "contributes a little bit," with the mix varying from patient to patient, he adds.

"Eventually, what we will be doing in this area is to profile more than a dozen genes in a patient to identify which treatments are most effective, a pattern that says this kind of patient should get inhaled steroids, or other kinds of treatment," Rosenwasser says.

Asthma is not the only disease in which genetic patterning will move into medical practice, he adds. The same kind of complex genetic interplay with environmental factors is to be found in a number of chronic conditions, Rosenwasser says.

It's to early to know how important T-bet is in human asthma, says Dr. Jeffrey M. Drazen, professor of medicine at Harvard Medical School and leader of the research team.

"It looks interesting, but we don't know its role for sure," Drazen says. "We know that humans with asthma have diminished expression of T-bet, but that doesn't mean that human asthma is characterized by a deficiency of T-bet."

The next step, he says, is to find out whether "if you did something to enhance expression of T-bet, would you make asthma better." That would require "something that works on that specific pathway, and we don't have it yet," Drazen says. His group will be looking for that something, he says.

Dr. Stephen Wasserman, chief of the allergy section at the University of California, San Diego, calls the finding "excellent work by a first-rate group," but adds a caution: "Mice ain't humans."

"We don't know whether we can interfere with this gene in humans," Wasserman, a past president of the American Academy of Allergy, Asthma and Immunology, says. "And we don't know whether we can interfere without causing mischief."

What To Do

With the payoff from this basic research years away, following the rules about limiting the problems caused by asthma is essential.

For basic information on asthma and its current treatment, consult the American Academy of Allergy, Asthma and Immunology. For more on the link between genetics and asthma, go to

SOURCES: Interviews with Lanny Rosenwasser, M.D., head, adult allergy, National Jewish Medical and Research Center, Denver, Stephen Wasserman, M.D., chief, allergy section, University of California, San Diego, and Jeffrey M. Drazen, M.D., professor of medicine, Harvard Medical School, Boston; Jan. 11, 2002, Science
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