Gene Found for Childhood Asthma
Reported January 05, 2010
(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 bodys 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