AsianScientist (Aug. 7, 2015) – Scientists 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.
The discovery, published in the American Journal of Human Genetics, provides a potential new treatment target, says study first author Dr. Manuel Ferreira from QIMR Berghofer’s Asthma Genetics laboratory.
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 percent,” 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.”
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.”
The article can be found at: Vicente et al. (2015) Long-Range Modulation of PAG1 Expression by 8q21 Allergy Risk Variants.
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Source: QIMR Berghofer Medical Research Institute; Photo: Shutterstock.
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