Unraveling the Genetic Roots of Anemia in Inflammatory Bowel Disease

Iron deficiency and anemia are common side effects of inflammatory bowel disease (IBD). A study by biomedical scientists at the University of California, Riverside School of Medicine found that a genetic mutation associated with Crohn’s disease can worsen these conditions.

IBD is a group of chronic inflammatory conditions, including Crohn’s disease and ulcerative colitis. While IBD primarily affects the intestines, it can also impact other organs. One of the most common complications is iron deficiency anemia. This condition often leads to ongoing fatigue and a reduced quality of life, especially during flare-ups.

The study used serum samples from IBD patients. It found that individuals with a loss-of-function mutation in the PTPN2 gene (protein tyrosine phosphatase non-receptor type 2) showed significant disruptions in blood proteins that regulate iron levels.

This mutation is found in 14–16 % of the general population and in 19–20 % of people with IBD. A loss-of-function mutation is a genetic change that weakens or eliminates the normal activity of a gene or its resulting protein.

This discovery sheds light on a critical mechanism that links a patient’s genetics to their ability to absorb and regulate iron, which is essential for maintaining healthy blood and energy levels. Our findings offer an explanation for why some IBD patients remain iron-deficient despite oral supplementation.

Declan McCole, Study Lead Investigator and Professor and Biomedical Sciences, University of California

When researchers removed the PTPN2 gene in mice, the animals developed anemia and showed poor iron absorption. This was linked to reduced levels of a key iron-absorbing protein found in intestinal epithelial cells, which play a central role in absorbing nutrients from food.

The only way the body can obtain iron is through intestinal absorption from food, making this discovery particularly significant. Disruption of this pathway by genetic variants like those in PTPN2 could help explain why some IBD patients fail to respond to oral iron therapy, a commonly prescribed treatment for anemia.

Hillmin Lei, Study First Author and Doctoral Student, University of California

McCole noted that the study helps clarify how genetic risk factors for IBD may worsen symptoms by disrupting nutrient absorption.

McCole added, “It opens new avenues for targeted therapies that go beyond inflammation control to address systemic complications like anemia. This includes prioritizing patients who carry loss-of-function PTPN2 variants to be treated for anemia with systemic intravenous iron supplementation rather than oral iron, which may be poorly absorbed.”