Ulcerative Colitis Gene Found – Newsweek

Scientists have identified a gene that can help doctors predict which patients are likely to develop severe ulcerative colitis.

The breakthrough, made by Danish researchers, means that for the first time, patients with ulcerative colitis who are likely to develop more severe disease can be identified—opening the way to earlier treatment.

At least six in every 1,000 people in the U.S., and in other Western countries, have ulcerative colitis, and the numbers are growing around the world. Scientists believe that the increase in the disease is primarily linked to the Western diet and lifestyle, although they have yet to pin it down to a single cause.

About 2 to 3 percent of people of European genetic ancestry carry a genetic variant linked to ulcerative colitis. It is similarly frequent in the Ashkenazi Jewish population, while data suggests a low frequency in Asian and African American populations.

When doctors see a patient newly diagnosed with chronic ulcerative colitis, it is usually difficult for them to predict whether that person will develop a mild disease or will require multiple hospitalizations, regular changes of medications and perhaps even major gastrointestinal surgery.

Gene Collection

Scientists in Denmark sought to investigate whether genes could provide an answer to this uncertainty. They collected genetic material on almost 4,500 Danish patients with ulcerative colitis and combined it with data from the Danish nationwide health care registers.

The most severe patients were identified based on information about hospitalizations, major surgery and treatment with steroids within the first three years after they were diagnosed.

More than 9 million genetic variants were then tested for any links they had with the severe ulcerative colitis group compared to the other ulcerative colitis patients.

“Essentially, you compare, one by one, if an individual genetic variant is more or less frequent among the severe group,” said Marie Vibeke Vestergaard, a doctoral student who conducted the research at the Center for Molecular Prediction of Inflammatory Bowel Disease (PREDICT) at Aalborg University in Denmark.

“Out of all of these variants, we detected a genetic variant called HLA-DRB1*01:03 to be strongly associated with several ulcerative colitis, confirming earlier smaller studies,” Vestergaard told Newsweek.

“When looking further into the different entities of our severity definition, we discovered that the variant associated with all three, but especially the need for major surgery, was highly correlated with the presence of the genetic variant,” she continued.

Professor Tine Jess, the director of PREDICT, was the senior scientist who led this research.

Reference

Vestergaard, M. V., Nøhr, A. K., Allin, K. H., Krarup, H., Larsen, L., Sazonovs, A., & Jess, T. (2024). HLA-DRB1*01:03 and Severe Ulcerative Colitis. JAMA. https://doi.org/10.1001/jama.2024.20429