New Insights on Genetic Factors Influencing Iron Deficiency in Crohn's Disease

A recent study conducted by scientists at the University of California, Riverside, has revealed a genetic mutation that may exacerbate iron deficiency and anemia in patients suffering from Crohn's disease, a common form of inflammatory bowel disease (IBD).

Crohn's disease is part of a broader category of chronic inflammatory disorders that primarily impact the gastrointestinal tract but can lead to systemic complications, including iron deficiency anemia. This condition is notably prevalent among IBD patients, contributing to significant fatigue and diminished quality of life, particularly during flare-ups.

The researchers analyzed serum samples from individuals diagnosed with IBD and found that those possessing a loss-of-function mutation in the PTPN2 gene (protein tyrosine phosphatase non-receptor type 2) experienced considerable alterations in blood proteins that manage iron levels. This particular mutation is observed in approximately 14-16% of the general population and in about 19-20% of IBD patients.

According to the study, the mutation leads to a reduction or complete loss of the normal function of the PTPN2 gene, which plays a crucial role in regulating iron absorption and overall blood health. The lead researcher emphasized that this discovery highlights a significant genetic mechanism affecting how patients absorb and manage iron, an essential element for maintaining energy levels and healthy blood.

Experiments involving mice that had the PTPN2 gene deleted demonstrated that these animals developed anemia and experienced difficulties in efficiently absorbing iron. The study indicated that this was due to decreased levels of a vital protein responsible for iron absorption in intestinal epithelial cells, which are critical for nutrient uptake from food.

Researchers pointed out that since iron can only be obtained through dietary absorption, the findings of this study are particularly significant. The disruptions caused by genetic variants such as those found in PTPN2 could elucidate why certain IBD patients do not respond to standard oral iron therapy, which is commonly prescribed for treating anemia.

The study opens up new possibilities for tailored treatments that extend beyond merely controlling inflammation in IBD patients. It suggests that those identified with loss-of-function mutations in PTPN2 might benefit from systemic intravenous iron supplementation rather than relying on oral iron, which may not be effectively absorbed by their bodies.

Published in the International Journal of Molecular Sciences, this research was conducted in collaboration with experts from City of Hope, University Hospital Zurich, and the Swiss IBD Cohort. The findings underscore the need to prioritize genetic considerations in developing treatment strategies for anemia in patients with inflammatory bowel disease.