New asthma gene identified

Scientists at QIMR Berghofer Medical Research Institute have found that a gene previously thought to have an anti-inflammatory effect, or no immune effect at all, is actually more likely to increase inflammation in people with asthma and allergies.

Dr Manuel Ferreira from QIMR Berghofer’s Asthma Genetics laboratory said the discovery provides a potential new treatment target.

The team is now seeking funds to develop drugs that block the PAG1 gene, and then test if these could reduce an asthma patient’s immune response to allergens.

“In a large genetic study last year we identified a previously unknown genetic variant which increased the risk of asthma and allergies by about 20 per cent,” Dr Ferreira said.

“It was not immediately obvious which gene that variant impacted, so we designed a series of molecular experiments to identify that target gene.

“We now know that while the risk variant is located a considerable distance from PAG1, it is able to reach that gene through a process known as DNA looping, and it increases PAG1 expression in people with asthma.”

Dr Ferreira said the latest research contradicts most previous studies on the function of the PAG1 gene in the immune system.

“In most of these studies – in animal models and human cell lines – there was no stimulation of the immune system with an allergen or virus, two key stimuli that trigger asthma,” he said.

“We believe that the function of PAG1 may be dependent on the context of the immune challenge – in the case of an allergen or virus it may have a pro-inflammatory response.

Dr Ferreira’s genetic work is highly regarded among international asthma researchers.

A variant he identified in 2011 has led to a clinical trial underway in Brisbane which is testing whether a drug used to treat rheumatoid arthritis could be useful in treating asthma.

“One in 10 Australians has asthma and it results in one death every day,” Dr Ferreira said.

“Not everyone is able to properly manage their symptoms with current preventers and treatments so it is vital that we look for new ways to help these people.

“Between 30 and 50 per cent of people have an allergy of some kind, often developed in their early years.”

The latest study was conducted in collaboration with Dr Stacey Edwards and Dr Juliet French at QIMR Berghofer and has been published in the respected American Journal of Human Genetics:
http://www.cell.com/ajhg/abstract/S0002-9297(15)00246-3