Abdominal pain, diarrhea, and debilitating fatigue define the daily lives of millions of people worldwide who suffer from chronic bowel disease. Most of these individuals are diagnosed in their youth, and the disease's progression can vary significantly, leaving patients uncertain about what the future holds. For some, ulcerative colitis is a manageable condition, while for others, it leads to frequent hospitalizations, complex medication regimens, and multiple surgeries.
Now, researchers from the Center for Molecular Prediction of Inflammatory Bowel Disease (PREDICT) at Aalborg University, have identified a genetic variant that may help predict which patients are likely to develop severe ulcerative colitis. Their study, just published in the Journal of the American Medican Association, JAMA, could guide more targeted treatment strategies.
"We have long known about this gene and its connection to colitis. However, we have now demonstrated that the same gene can predict whether a patient will require more intensive treatment, including higher medication doses or major surgery. This knowledge is critical as we aim to tailor treatments more effectively," says PhD student and lead author, Marie Vibeke Vestergaard.
More Aggressive Treatment from the Outset
The study, which analyzed both genetic data and Danish health records, found that around three percent of patients with ulcerative colitis carry a specific genetic variant – HLA-DRB1*01:03. Among this group, over 40 percent underwent major gastrointestinal surgery within the first three years of diagnosis—compared to only nine percent of those without the variant.
"This is a group of patients who are especially hard-hit by the disease," says Vestergaard.
"In cases of ulcerative colitis, early intervention is essential to prevent the disease from progressing and damaging the intestines. Our hope is that this discovery will allow doctors to closely monitor these patients from the very start, potentially administering more aggressive treatment early on."
Vestergaard explains that preventing disease progression could not only improve patient outcomes but also reduce societal healthcare costs.
"By targeting treatment more precisely from the beginning, we can avoid the inefficiencies of trial-and-error approaches," she adds.
A Significant Genetic Effect
Head of Genomics at PREDICT, Associate Professor Aleksejs Sazonovs, was surprised by the strength of the findings, noting the substantial impact of a single genetic variant.
"I'm extremely proud of the work we've done at PREDICT, demonstrating how Denmark's unique health data and biobank resources can benefit patients worldwide. As rates of inflammatory bowel diseases continue to rise in Western countries, the more we understand about the underlying genetics, the better we can treat and prevent these conditions."
Sazonovs emphasized that while the results are promising, they must be validated through external studies. The next step will involve clinical trials to assess the impact of intensified monitoring and early treatment in patients with the genetic variant.
FURTHER INFORMATION
Ulcerative Colitis Overview
Ulcerative colitis is a chronic inflammatory bowel disease, commonly affecting young individuals. In the US alone, around 750,000 people are affected by the disease. The severity and progression of the disease vary greatly from person to person. While some experience only mild symptoms, others endure more severe cases, involving frequent hospitalizations, changes in medications, and, in some instances, surgery to remove affected parts of the intestine.
In some patients, symptom-free periods may last for an extended time, but relapses are common. The unpredictable nature of the disease means it's often unclear whether a particular treatment is effective.
Research Findings
Researchers have identified a specific genetic variant, HLA-DRB1*01:03, which is strongly associated with severe cases of ulcerative colitis. Around 3% of patients with ulcerative colitis carry this variant. Among these individuals, over 40% required major gastrointestinal surgery within the first three years after diagnosis, compared to only 9% of those without the variant.
About PREDICT
Denmark's Basic Research Foundation has allocated DKK 68.5 million to support the Center for Molecular Prediction of Inflammatory Bowel Disease (PREDICT) at Aalborg University (AAU).
