Long noncoding RNA tied to celiac disease susceptibility

Last Updated: 2016-04-12

By David Douglas

NEW YORK (Reuters Health) - Long noncoding RNAs (lncRNAs) are implicated in celiac disease, and U.S. and Spanish researchers are shedding more light on the role of lnc13 in the underlying processes.

"These findings," Dr. Sankar Ghosh told Reuters Health by email, "add an important detail to our understanding about how celiac disease develops."

This is of particular interest, according to the investigators, because although an estimated 40% of the population has the primary gene variant associated with celiac disease, only 1% go on to develop intestinal inflammation and damage from ingesting gluten.

In an April 1 online paper in Science, Dr. Ghosh, of Columbia University Medical Center, New York, and colleagues report that following preliminary work in mice they confirmed expression of lnc13 in humans.

They then determined that, compared to controls, biopsies from celiac disease patients showed "substantially lower" amounts of lnc13. Quantification of levels of lnc13 in intestinal biopsies of patients with celiac disease showed significantly down-regulation compared with healthy controls.

To further characterize lnc13, the team stimulated mouse bone marrow-derived macrophages with lipopolysaccharide (LPS) to mimic an inflammatory environment. Consistent with observations in celiac disease patients, "the level of lnc13 decreased significantly upon LPS stimulation."

They then went on to compare expression changes of lnc13 with those of 92 protein-coding genes with established inflammatory roles. After LPS stimulation, expression of four of these genes (TRAF2, STAT1, IL1RA, and MYD88) was significantly increased in biopsies from celiac disease patients.

These and other studies showed that lnc13 was able to regulate the expression of a subset of celiac disease-associated inflammatory genes through interaction with chromatin and the multifunctional protein hnRNPD, a member of a family of ubiquitously expressed heterogeneous nuclear ribonucleoproteins.

Moreover, wrote the investigators, "The lnc13 disease-associated variant binds hnRNPD less efficiently than its wild-type counterpart, thus helping to explain how single-nucleotide polymorphisms contribute to celiac disease."

Summing up, Dr. Ghosh added, "Given that the majority of the population consumes grains that contain gluten, including wheat, barley, and rye, understanding the factors that put certain individuals at greater risk for the development of celiac disease will have a broad impact."

"In future studies," he concluded, "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."

Commenting on the findings by email, Dr. David van Neel, leader of the celiac disease genetics research group at Barts and the London School of Medicine and Dentistry, told Reuters Health that the team "found a new mechanism explaining how a chronic human immune disease genetic risk variant might cause inflammation."

The Spanish government and other organizations supported this research. The authors made no disclosures.

SOURCE: http://bit.ly/1pOgyfh

Science 2016.