A team of international researchers have pinpointed a specific gene after studying more than 2,000 children - 994 with childhood asthma and 1,243 non-asthmatics.
The gene called ORMDL3 was found at higher levels in the blood cells of children with asthma and the team believe carrying a specific variant of this gene may increase the risk of developing asthma by up to 70%.
The researchers led by Imperial College London also identified genetic markers on chromosome 17 which appeared to alter levels of ORMDL3.
Asthma is one of the most common chronic childhood diseases and affects one in seven children, however despite it's prevalence the combination of genetic and environmental factors which cause it are still unclear.
Dr. Miriam Moffatt, from Imperial College's National Heart and Lung Institute, says the large study involving scientists and doctors from many countries, has revealed something new and exciting about childhood asthma and adds to the gene environment jigsaw that makes up the disease.
Professor William Cookson, another team member says the results provided the strongest genetic effect on asthma so far discovered but it still remains unclear how ORMDL3 increases the risk of asthma.
Professor Cookson says similar genes are found in primitive organisms such as yeast, and they suspect that ORMDL3 may be a component of quite ancient immune mechanisms but it does not seem to be part of the allergic process.
The team examined mutations in the building blocks, called nucleotides, which make up DNA; as there are mutations in around one in every 600 nucleotides, the scientists examined more than 317,000.
Asthma charities have welcomed the research and say the gene discovery is an exciting development.
The research is published in the journal Nature.
GLIS2 normally prevents cell death in the adult kidney. It does so by shutting down genes that initiate cell death and that are only required during the development of the organ. A mutation interfering with GLIS2 function reactivates these harmful genes the result being that large numbers of kidney cells die. The organ shrinks and changes in its architecture occur which affect normal kidney function.
To find out if GLIS2 has the same effect in humans Friedhelm Hildebrandt and his team at the University of Michigan carried out a genetic screen of patients suffering from NPHP. They found that like the mouse model some patients carried mutations in the same GLIS2 gene, confirming that GLIS2 is a crucial player in NPHP also in humans.
"This is an excellent example of how combining basic research with clinical studies can help uncovering mechanisms of human disease," says Henriette Uhlenhaut who carried out the research in Treier's lab. "The next step will be to translate the insights gained into new therapeutic approaches to develop alternatives to kidney transplantations. With GLIS2 we have already identified one promising candidate drug target and our mouse model will help us find many others."
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