Gene linked to childhood asthma identified

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London, December 24 (ANI): Researchers have identified a gene linked to childhood asthma, a finding that may be instrumental in developing new treatments for common respiratory disease.

The team led by Hakon Hakonarson, M.D., Ph.D., director of the Center for Applied Genomics at The Children's Hospital of Philadelphia, found the gene, called DENND1B, which affects cells and signaling molecules thought to be instrumental in the immune system overreaction that occurs in asthma.

Earlier U.K study had identified only one other asthma-susceptibility gene ORMDL3, on chromosome 17, using a genome-wide association study (GWAS), in which automated genotyping tools scan the entire human genome seeking gene variants that contribute to disease risk.

Hakonarson's team also performed GWAS on a sample of 793 white North American children with persistent asthma, compared to 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.

They found a novel location on chromosome 1q31, with eight single nucleotide polymorphisms (SNPs) associating robustly with asthma. A SNP is a change to a single chemical base along the DNA helix. Unlike other studies, here the researchers found the same gene for asthma susceptibility in children of both European and African-American ancestries.

Within this region on chromosome 1q31 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 particular types of dendritic cells and specific T lymphocytes, including natural killer cells.

Both of these immune cell subtypes form cross-talks between them (commonly referred to as the antigen presenting synapse) and regulate how the body responds to foreign material such as viruses, bacteria and allergens.

Hakonarson said: "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."

"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.

"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.

"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 hyperresponsiveness. The gene mutations in DENND1B appear to lead to overproduction of cytokines that subsequently drive this oversensitive response in asthma patients. "

He concluded: "Because this gene seems to regulate many different cytokines, intervening in this pathway has great potential for treating asthmaOther asthma-related genes remain to be discovered, but finding a way to target this common gene variant could benefit large numbers of children."

The study will be published on the New England Journal of Medicine in January 2010. (ANI)

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