New Genetic Culprit in Asthma Found

People with it are likelier to suffer breathing problems

By Adam Marcus HealthDay Reporter

Updated on June 15, 2022

WEDNESDAY, July 10, 2002 (HealthDayNews) -- Researchers have found a gene that appears to increase the odds a person will develop asthma.

Scientists had previously discovered so-called asthma susceptibility genes in animals, and had drawn a bead on the general location of some of these instructions in humans. However, the new work, reported in tomorrow's online issue of Nature, is the first to identify a specific asthma gene in a large and relatively diverse group of people.

The team of British and American researchers say it's too soon to tell how potent a risk factor the gene, called ADAM33, will prove to be. For now, the most they can say is that having variants of the gene appear to up the odds of suffering lung trouble.

Knowing which genes predispose a person to asthma could one day help treat or even prevent the disease, which affects 10 million adults and 5 million children in this country. More than 4,600 people died of the lung disease in 1999, according to the Centers for Disease Control and Prevention.

"It really should allow the development of therapies that would target the disease process, [unlike] existing therapies, which target symptoms," says study co-author Tim Keith, senior director of human genetics at Genome Therapeutics, a biotech firm in Waltham, Mass.

Keith and her colleagues looked for asthma genes in 460 white families from the United Kingdom and the United States in which at least two children had the airway ailment. Overall, some 2,000 people participated in the study, and roughly 1,000 had asthma.

The group identified 135 variations of 23 genes possibly associated with asthma. Variants of one of those, ADAM33, had the strongest tie to the disease.

Residing on chromosome 20p13, ADAM33 encodes proteins that prompt cell surfaces to shed other proteins, including immune molecules and the receptors that recognize and respond to them. Asthma leads to thickening and narrowing of the airway walls, and the researchers speculate that ADAM33 may somehow encourage this process.

Keith's group also found an association between variants of ADAM33 and hyperactive airways -- a condition known as bronchial hyper-responsiveness.

Genome Therapeutics has partnered with drug maker Schering-Plough, of Kenilworth, N.J., to convert their gene screening into an asthma treatment. Keith says the pharmaceutical company is now analyzing chemicals in bulk to see which, if any, interact with ADAM33.

Asthma experts caution the disorder is extremely complex.

Dr. Dale Umetsu, a Stanford University pediatrician who studies the genetics of asthma, says a dozen or so genes likely cause the disease. These may make people more vulnerable to environmental irritants like cockroaches, cigarette smoke and air pollution. That asthma rates have spiked in recent years reflects the importance of these environmental forces, he says.

However, susceptibility genes may work to promote lung problems in other ways, too.

Umetsu calls ADAM33 an important player in the genetics of asthma, but adds it's still something of a mystery to researchers.

"It's a relatively unknown gene, and if one can find out how it works one could figure out better therapies to enhance the disabled function or reduce the enhanced function" of the instruction, he says.

What To Do

To learn more about asthma, try the Centers for Disease Control and Prevention or the Allergy and Asthma Foundation of America.

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