Four Genetic Variants Common to Celiac Disease and Crohn's


Celiac disease and Crohn’s disease are two separate conditions which affect the function of the bowel, but those who have celiac appear to have a higher rate of Crohn’s than the general population. Researchers have discovered four genetic variants that tie the two disorders together which could one day lead to new treatments for both.

Three of Four Genes Involved in Immune System Response

Celiac disease is an autoimmune disorder where the lining of the intestine becomes damaged by a reaction to gluten, a protein found in wheat, rye and barley. The resulting damage prevents the intestine from absorbing nutrients appropriately, leading to complications such as anemia and malnutrition.

Crohn’s disease is an inflammation of the digestive tract that can cause the bowel to empty frequently, resulting in diarrhea. Although the exact cause of Crohn’s is unknown, the condition is also linked to a problem with the body’s immune system response.

Previous research has shown that more than 18.5% of patients with Crohn’s disease also have Celiac disease.

Read: Living Gluten-Free in a Wheat World

Study Co-Author John D. Rioux PhD and an international team of researchers compared 471,504 single nucleotide polymorphisms (SNPs) representing the genomes of about 10,000 people. Four genes appeared to contribute to the risk for both Celiac and Crohn’s disease.


Two of the genes, IL18RAP and PTPN2, were previously known to be associated with each condition. IL18RAP, also known as interleukin 18 receptor accessory protein, encodes a gene for a receptor of immunoglobulins. PTPN2 encodes an enzyme called tyrosine-protein phosphatase non-receptor type 2, which are signaling molecules that regulate a variety of cellular processes including cell growth.

Read: Crohn's Disease Responds to Vitamin D Supplements

The third gene, called TAGAP, had previously been identified as an area of risk in Celiac disease, but was newly found to increase risk for Crohn’s. This gene, also known as T-cell activation RhoGTPase activating protein, is also associated with insulin-dependent diabetes mellitus.

“The first three we can say are involved in T-lymphocyte function,” said Dr. Rioux, an associate professor of medicine at the University of Montreal. “They seem to have a role to play in how these cells respond to a given stimulus.”

The fourth gene, PUS10 or pseudouridylate synthase 10, had also been tied to both Crohn’s and Celiac disease, but may play a different role than the first three.

At least one in every hundred individuals in the Western world develops Celiac disease. Crohn's disease is much less common but can be accompanied by more severe symptoms as it can affect the whole gastrointestinal tract.

Journal Reference:
Eleonora A. M. Festen, Philippe Goyette, Todd Green, Gabrielle Boucher, Claudine Beauchamp, Gosia Trynka, Patrick C. Dubois, Caroline Lagacé, Pieter C. F. Stokkers, Daan W. Hommes, Donatella Barisani, Orazio Palmieri, Vito Annese, David A. van Heel, Rinse K. Weersma, Mark J. Daly, Cisca Wijmenga, John D. Rioux. A Meta-Analysis of Genome-Wide Association Scans Identifies IL18RAP, PTPN2, TAGAP, and PUS10 As Shared Risk Loci for Crohn's Disease and Celiac Disease. PLoS Genetics, 2011; 7 (1): e1001283 DOI:10.1371/journal.pgen.1001283