Penn Research Provides Better Understanding into How Genes Make Us Prone To Allergies

PHILADELPHIA— New research is bolstering scientific understanding behind why some people are more prone to allergies than others. Researchers in the Perelman School of Medicine at the University of Pennsylvania identified how genetic differences that alter a specific protein called ETS1 can affect our body’s response to allergies. They found that small changes in ETS1 in an animal model can lead to an increased likelihood for allergic reactions that cause inflammation. The findings were published recently in Immunity.

The United States Centers for Disease Control and Prevention reports that allergies rank as the sixth most prevalent cause of chronic illness in the U.S., resulting in an annual expenditure exceeding $18 billion. While previous research has established a strong genetic basis for allergies and identified specific genetic sequence variations which predispose for these chronic diseases, how our DNA can affect our chances of developing an allergy remains unclear. But understanding this could lead to improved research and potential new treatments.

By using modern genomics and imaging techniques, a collaborative team of researchers co-led by Penn’s Golnaz Vahedi, PhD, an associate professor of Genetics, and Jorge Henao-Mejia, MD, PhD, an associate professor of Pathology and Laboratory Medicine, found that the ETS1 protein plays a role in controlling a type of immune cell called CD4+ T helper cells, which are important in allergic reactions and help orchestrate the immune response by activating and coordinating other immune cells.

DNA interactions within the genomic segment encompassing the ETS1 gene control how much of the ETS1 protein is made. 

“We discovered that these interactions, work like a dimmer switch,” said Vahedi. “When there are changes in the DNA in this area, it can mess up the dimmer switch, causing problems with controlling the ETS1 protein. This can lead to imbalances in our immune cells and cause allergic inflammations.”

While there has been progress in understanding genetic traits that follow predictable patterns, like those passed down from parents, it’s been more challenging to understand conditions that involve many different genes and are common in populations. These complex conditions cannot be explained by simply “turning off” one gene. Instead, they may be caused by small changes in the DNA that affect how genes work together. However, researchers still do not know much about how these changes in DNA relate to how our genes are organized or how they affect how genes are expressed in most complex diseases.

“This work demonstrates how small differences in our DNA can disturb the balance between our immune cells, resulting in significant observable characteristics in patients. This phenomenon may occur in other common diseases such as autoimmune disorders,” said Henao-Mejia.

Other co-authors of this study include Aditi Chandra, Sora Yoon, and Michael Michieletto. This research was funded by the National Institutes of Health (R01AI168240, UC4 DK112217, U01 DK112217, R01 HL145754, U01 DK127768, U01 DA052715, R01 HL136572), the Burroughs Welcome Fund, the Chan Zuckerberg Initiative Award, W. W. Smith Charitable Trust, the Sloan Foundation, and the PEW Charitable Trust.

 

###

Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation’s first medical school) and the University of Pennsylvania Health System, which together form a $8.9 billion enterprise.

The Perelman School of Medicine is consistently among the nation’s top recipients of funding from the National Institutes of Health, with $546 million awarded in the 2021 fiscal year.

The University of Pennsylvania Health System’s patient care facilities include: the Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center—which are recognized as one of the nation’s top “Honor Roll” hospitals by U.S. News & World Report—Chester County Hospital; Lancaster General Health; Penn Medicine Princeton Health; and Pennsylvania Hospital, the nation’s first hospital, founded in 1751. Additional facilities and enterprises include Good Shepherd Penn Partners, Penn Medicine at Home, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others.

Penn Medicine is powered by a talented and dedicated workforce of more than 44,000 people. The organization also has alliances with top community health systems across both Southeastern Pennsylvania and Southern New Jersey, creating more options for patients no matter where they live.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2020, Penn Medicine provided more than $563 million to benefit our community.

withyou android app