New risk factor for celiac disease identified in non-coding RNA

Researchers have identified a non-coding RNA gene variant that appears to promote the intestinal inflammation that occurs in people with celiac disease. This finding suggests a possible new risk factor that makes people with celiac disease genes more susceptible to developing the disease, according to a study published online in the journal Science.

“These findings add an important detail to our understanding about how celiac disease develops,” said the study’s lead author Sankar Ghosh, PhD, the Silverstein and Hutt Family Professor of Microbiology and Immunology, Chairman of the Department of Microbiology and Immunology at Columbia University Medical Center (CUMC), in New York, NY.

An estimated 40% of the population has the primary gene variant associated with celiac disease, but only 1% of people with these genes go on to develop intestinal inflammation and damage after ingesting gluten.

For this study, the researchers focused on long non-coding RNAs (lncRNA), which make up large (and largely unexplored) portions of the genome that do not code for proteins, but likely have other functions. Previous genome-wide association studies located various single nucleotide polymorphisms (SNPs) related to celiac disease, some of which appeared among non-coded RNA.

Through a combination of experiments, the researchers found a specific long non-coding RNA—lnc13—that normally dampens the expression of the inflammatory genes associated with celiac disease. But when the celiac-associated variant of lnc13 was stimulated, levels of lnc13 decreased, the researchers found. Consequently, this decrease in lnc13 allowed increased expression of the repressed genes, which led to inflammation in the intestine.

To further investigate this, the researchers analyzed small intestinal biopsies from patients with celiac disease. They discovered that these patients had unusually low levels of lnc13, which suggests that the downregulation of lnc13 contributes to the intestinal inflammation seen in celiac disease.

“In future studies, we hope to investigate factors that lead to suppression of lnc13, which may cause celiac disease in people who were previously able to tolerate gluten,” Dr. Ghosh said.

Further research might also reveal previously unidentified targets for diagnosing or treating such inflammatory conditions as celiac disease, the researchers predicted.

“Given that the majority of the population consumes these grains, understanding the factors that put certain individuals at greater risk for the development of celiac disease will have a broad impact,” Dr. Ghosh said.