Can Iron Supplementation Protect Against Celiac Disease?

TOPLINE:

Genetically lower iron levels were associated with an increased risk for celiac disease, pointing to a potential opportunity to prevent the disease, new data suggested.

METHODOLOGY:

Iron deficiency, which is common in celiac disease, has been proposed as an environmental trigger for the disease that has been growing in prevalence. To investigate, researchers conducted a Mendelian randomization study examining the relationship between single nucleotide polymorphisms (SNPs) associated with iron status and the presence of celiac disease. SNPs were drawn from a meta-analysis of three genome-wide association studies. Their association with celiac disease was assessed using data from 336,638 White UK Biobank participants, including 1855 with celiac disease.

TAKEAWAY:

Four SNPs were strongly and independently associated with systemic iron status: rs1800562 and rs1799945 in the hemochromatosis gene, rs855791 in the transmembrane protease serine 6 gene, and rs57659670 predicted to affect the Dual Oxidase 2 gene. None were associated with known celiac disease risk factors. Higher iron status was negatively associated with celiac disease risk (odds ratio per 1 SD increase in serum iron: 0.65). No single SNP appeared to drive the association in sensitivity analyses. By relying on SNPs associated with iron status, and not on iron status itself, this Mendelian randomization analysis suggests a causal effect of iron deficiency on subsequent celiac disease development.

IN PRACTICE:

“These findings suggest that iron supplementation in select individuals may provide a potential protective effect against celiac disease development,” the authors wrote.

SOURCE:

The study, with first author Isabel A. Hujoel, MD, a gastroenterologist with University of Washington, Seattle, was published online on January 4, 2024, in BMJ Open Gastroenterology.

LIMITATIONS:

Researchers used a PheCode to identify celiac disease cases, which could lead to misclassification. Mendelian randomization provides some protection against biases, such as reverse causation, but is not completely invulnerable.