Genetic Marker Could Identify Patients With Severe Inflammatory Bowel Disease

In the largest genetic study of inflammatory bowel disease (IBD) traits to date, researchers have identified a genetic marker that is associated with more severe ulcerative colitis and Crohn’s disease – the major forms of IBD.

Researchers from the Wellcome Sanger Institute, the Francis Crick Institute and the NIHR IBD BioResource genetically analysed samples from over 43,000 patients from more than 100 hospitals.

For the first time, the team identified a combination of genetic variants within the HLA-DRB1 gene – known collectively as HLA-DRB1*01:03 – that is associated with more severe disease in people living with IBD.

The results, published in The Lancet Gastroenterology and Hepatology, suggest that genetic testing could identify IBD patients at risk of severe disease, meaning they could be monitored more closely and given advanced therapies earlier.

Over half a million people in the UK are estimated to be living with Crohn’s disease and ulcerative colitis¹. These are painful, debilitating and lifelong conditions with no known cure, which cause ulceration and inflammation in the gut.

Treatments for Crohn’s disease and ulcerative colitis depend on how severe the symptoms are and how much of the gut is affected. Patients are given medicines that reduce inflammation in the gut, including immunosuppressants and monoclonal antibody therapies, and in more severe cases, surgery may also be required².

The course of disease in IBD is very unpredictable. Some patients experience mild symptoms, including diarrhoea, cramps and fatigue, while others have frequent flare ups or develop much more severe disease that significantly impairs their quality of life.

To understand the role of genetics in IBD, Sanger Institute scientists and their collaborators studied data from 43,762 patients from the NIHR IBD BioResource and UK IBD Genetics Consortium³ – including 21,839 individuals with Crohn’s disease and 21,923 individuals with ulcerative colitis or unclassified IBD.

The researchers found that HLA-DRB1*01:03 was present in approximately one in 20 IBD patients and associated with multiple severe outcomes. This included the need for removal of part or all of the colon in those with Crohn’s disease and ulcerative colitis as well as individuals with perianal disease – a condition affecting the skin and tissue around the anus. There was also increased need for advanced therapies in patients positive for HLA-DRB1*01:03.

Genetic testing of patients to see if they carry this combination of genetic variants could help identify those who are predisposed to more severe IBD, so that they can be monitored closely and given advanced treatments earlier.