Protein form linked to severe COVID-19 and lung disease risk

Led by the University of Edinburgh, the study identified a previously unknown lung-specific form of the DPP9 protein, which plays an important role in regulating inflammation. The newly identified protein form contains a common genetic variant carried by almost one in three people.

The researchers found that this lung-specific form of DPP9 differs in both shape and function from the standard DPP9 protein found throughout the body. Their findings suggest that these differences may influence how the lungs respond to inflammation and could help explain the increased risk of severe COVID-19 and lung fibrosis associated with the genetic variant.

The Centenary Institute’s Professor Mark Gorrell and Jasmine Minh Hang Nguyen were co-authors on the collaborative study.

Professor Gorrell, who discovered DPP9 in 1999, said the findings highlight the importance of looking beyond conventional genetic approaches.

“Most genetic studies focus on the standard form of a gene. This work shows that genetic variants can lie in alternative protein forms that also play an important role in disease and which have largely been overlooked,” he said.

“The newly identified DPP9 protein form is found specifically in the lung and provides new insights into why some people are more susceptible to severe lung inflammation, fibrosis and infectious disease. It also demonstrates the power of new technologies to reveal previously hidden aspects of human biology.”

The study, published in the journal Nature Communications, also uncovered a number of previously unrecognised protein forms across the human genome, suggesting that alternative protein forms may play a broader role in human health and disease than previously recognised.