(Ivanhoe Newswire) -- Pediatric researchers have identified a gene
which may provide an important target for new childhood asthma treatment.
Asthma is a complex disease in which a large number of genes are thought to
interact with one another and with environmental factors to produce asthma's
characteristic wheezing, coughing and shortness of breath. The disease
manifests differently in different patients, and appears to operate
differently in childhood-onset asthma compared to adult-onset asthma.
A team led by Hakon Hakonarson, M.D., Ph.D., director of the Center for
Applied Genomics at The Children's Hospital of Philadelphia, performed a
genome-wide association study (GWAS) on 793 white North American children
with persistent asthma, comparing them to a control group of 1,988 children.
They replicated the study in a separate group of 2,400 European subjects and
controls, then did further analyses on a third group of 3,700 African
American children.
"By analyzing a large cohort of children with moderate to severe asthma, all
of whom require controller medications on a regular basis, we managed to
enrich our study for genetic signals and achieve sufficient statistical
power to uncover and replicate a novel asthma gene," Hakonarson was quoted
as saying.
The gene with an apparent role in asthma is DENND1B, already suspected as a
player in the body's immune response. DENND1B expresses a protein of the
same name, which is active in immune cell subtypes that regulate the body’s
response to foreign bodies such as viruses, bacteria and allergens. The
researchers found the same gene for asthma susceptibility in children of
European and African-American ancestries.
"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," said Hakonarson. "Many
of these particles are well-known triggers of asthma. 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 hyper-responsiveness. The gene mutations in DENND1B appear to lead to
overproduction of cytokines that subsequently drive this oversensitive
response in asthma patients."
Hakonarson believes his team may have pinpointed a potential therapeutic
target, if researchers can develop drugs to contain this signaling pathway.
"Because this gene seems to regulate many different cytokines, intervening
in this pathway has great potential for treating asthma," he added. "Other
asthma-related genes remain to be discovered, but finding a way to target
this common gene variant could benefit large numbers of children."
SOURCE: New England Journal of Medicine, January 7, 2010
