Epigenetic Study Finds New Potential Drug Targets for Asthma and Allergies

A new epigenetic study has identified 30 genes connected to allergies and asthma that make people more susceptible to these conditions. Using the newly discovered gene targets from this study, scientists could potentially create drugs to combat allergic diseases and reduce allergic responses.

About 6.8 million children and 18.7 million adults in the U.S. suffer from asthma. According to the Asthma and Allergy Foundation of America, 60 million people suffer from both asthma and allergies, affecting 1 out of every 5 Americans. The results from this new study could help these individuals by creating novel treatments for these diseases and by predicting whether or not some people will respond successfully to treatments that are currently available.

This 10-year-long study was recently published in Nature and was headed by scientists at Imperial College London. It also involved other scientists in Canada, the United States, and Sweden who utilized their expertise in new methods for studying genes linked to the immune system. The research team investigated epigenetic changes in hopes of identifying new therapeutic targets.

The antibody, immunoglobulin E (IgE), is crucial to immune defense and plays a role in triggering a response to allergens. This new study was able to identify the genes that are responsible for regulating this antibody, something which had not previously been done before.

The researchers investigated DNA methylation, or the process by which a methyl group is added onto DNA which can often silence certain genes. Specifically, they analyzed peripheral blood leukocytes, or white blood cells, of families with asthma from the United Kingdom to find out if certain levels of methylation at various locations of their genome were correlated with the amount of IgE found in the blood. To take it a step further, the researchers also tested whether the DNA methylation levels were the same for other volunteers from Wales with low and high amounts of IgE as well as for other families from Quebec who suffer from asthma.

The results indicated a strong connection between low DNA methylation levels at 36 places in 34 genes and IgE levels. These 34 genes are too active in people with asthma, which causes them to make more IgE and develop symptoms of asthma.

The genes related to IgE are known to implicate phospholipid inflammatory mediators and some IgE-related genes encode for proteins produced by a certain form of white blood cell – known as eosinophils – that enhances inflammation in the airways of people who suffer from asthma. The scientists think that the genes could turn on the eosinophils and cause the largest degree of damage. To put their hypothesis to the test, they took eosinophils from the blood of 24 people and demonstrated that all of the 34 genes are most active in people with asthma who have high IgE levels.

There are already treatment options for neutralizing eosinophils, but they are extremely costly and not effective for everyone. These results point us in the right direction for finding out who will respond positively to this therapy before actually starting it.

Professor Miriam Moffatt from the National Heart & Lung Institute at Imperial College who led the study said, “The genes we identified represent new potential drug targets for allergic diseases as well as biomarkers that may predict which patients will respond to existing expensive therapies.”

Professor Cookson from the National Heart & Lung Institute at Imperial College who also led the study explained the use of epigenetic techniques in advancing scientific discoveries: “Our pioneering approach, using epigenetics, allowed us to obtain insights that we weren’t able to get from traditional genetics. It isn’t just the genetic code that can influence disease and DNA sequencing can only take you so far. Our study shows that modifications on top of the DNA that control how genes are read may be even more important.”

Source: Learn all about it and read more about their findings here: An epigenome-wide association study of total serum immunoglobulin E concentration. Liming Liang, Saffron A. G. Willis-Owen, Catherine Laprise, Kenny C. C. Wong, Gwyneth A. Davies, Thomas J. Hudson, Aristea Binia, Julian M. Hopkin, Ivana V. Yang, Elin Grundberg, Stephan Busche, Marie Hudson, Lars Rönnblom, Tomi M. Pastinen, David A. Schwartz, G. Mark Lathrop, Miriam F. Moffatt, William O. C. M. Cookson. Nature. 2015.

References: Imperial College London. Epigenetic study highlights drug targets for allergies and asthma. 18 Feb 2015.

Centers for Disease Control and Prevention. Asthma. 2015.

Asthma and Allergy Foundation of America. Allergy Facts and Figures. 2015.