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New Gene Tied to Childhood Asthma

Researchers Say Identification of Gene May Lead to Development of New Treatments

By Jennifer Warner
WebMD Health News

Reviewed By Brunilda Nazario, MD

Dec. 28, 2009 -- A newly identified gene may play a critical role in triggering childhood asthma and offer new opportunities for developing more effective asthma treatments.

Researchers say the gene, DENND1B, affects cells and other signaling molecules thought to be involved in the immune system overreaction that occurs in childhood asthma.

"We now know that the DENND1B gene and its protein are involved in the release of cytokines, which are signaling molecules that in this case tell the body how it should respond to foreign particles," says researcher Hakon Hakonarson, MD, PhD, director of the Center for Applied Genomics at The Children's Hospital of Philadelphia, in a news release. "In asthma, patients have an inappropriate immune response in which they develop airway inflammation and overreaction of the airway muscle cells, referred to as airway hyperresponsiveness. The gene mutations in DENND1B appear to lead to overproduction of cytokines that subsequently drive this oversensitive response in asthma patients."

Asthma is a complex disease that causes wheezing, coughing, and shortness of breath.

Researchers say many factors, including genetics and environmental factors, play a role in the cause of asthma. Until now, only one gene has been associated with childhood asthma, but many genes are thought to be involved.

In the study, researchers scanned the entire human genome looking for gene variants associated with childhood asthma risk in 793 white North American children with persistent asthma and a comparison group of 1,988 healthy children.

To confirm their results, published in the New England Journal of Medicine, they then replicated the study in another group of 2,400 people of European ancestry and 3,700 African-American children.

In addition to confirming the previously identified asthma gene located on chromosome 17, researchers found another gene located on chromosome 1q31 was associated with an increased risk of childhood asthma in both children of European and African ancestry.

Researchers say the gene, DENND1B, is already suspected to be involved in the body's immune response and helps regulate how the body responds to foreign substances, like viruses, bacteria, and allergens.

"Intervening in this pathway has great potential for treating asthma," says Hakonarson. "Other asthma-related genes remain to be discovered, but finding a way to target this common gene variant could benefit large numbers of children."

SOURCES: Sleiman, P. New England Journal of Medicine, Dec. 28, 2009 online first edition.

News release, Children's Hospital of Philadelphia.

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