New Gene Tied to Childhood Asthma

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."



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