Study Discovers Link Between Celiac Disease Risk and a Noncoding RNA
Suggests factors outside of protein-coding genes play a role in celiac disease
Researchers have identified a segment of RNA that, when suppressed, may contribute to the intestinal inflammation that occurs in people with celiac disease. The findings point to a possible new risk factor for celiac disease.
The study was the result of a multi-institutional, multidisciplinary collaboration between the Celiac Disease Center and researchers at Columbia University’s department of Microbiology and Immunology. The findings are reported in Science.
Celiac disease is an autoimmune digestive disorder in which genetically predisposed individuals develop an immune response to gluten, a protein found in cereal grains, wheat, rye and barley. An estimated 40 percent of the population has the gene variants associated with celiac disease, but only 1 percent of people with these genes go on to develop intestinal inflammation and damage—the hallmarks of the disease—after ingesting gluten.
“We don't know why only a fraction of individuals with genetic risk factors for celiac disease actually become gluten intolerant,” said Peter Green, MD, the Phyllis and Ivan Seidenberg Professor of Medicine at Columbia University Medical Center (CUMC), director of the Celiac Disease Center at Columbia University, gastroenterologist at NewYork-Presbyterian/Columbia and a lead author of the paper. “Through the dedicated work of translational scientists, we are beginning to uncover the mechanisms that unleash the symptoms of celiac disease and identify potential therapeutic targets.”
Previous studies have identified a number of risk genes responsible for making proteins that are associated with the disease. Recently, researchers have focused on the ability of noncoding RNA, the portion of our genome that does not contribute to the production of proteins, to regulate a variety of biological processes. Long noncoding RNA (lncRNA), which contains more than 200 nucleotides, is thought to play a role in autoimmune diseases and cancers by interacting with other RNA, DNA, and proteins.
Through a variety of experiments, the researchers demonstrated that lnc13 dampens the expression of celiac-associated genes by binding to a common family of proteins. They then discovered that patients with celiac disease had unusually low levels of lnc13 in their intestines, suggesting that reduced levels of this RNA may contribute to the inflammation seen in celiac disease by turning off the normal regulatory pathway.
“These findings add an important detail to our understanding about how celiac disease develops,” said Sankar Ghosh, PhD, the Silverstein and Hutt Family Professor of Microbiology and Immunology, chairman of the Department of Microbiology and Immunology at CUMC and another lead author. “Given that the majority of the population consumes these grains, understanding the triggers for the development of celiac disease will have a broad impact. In future studies, we hope to investigate factors that lead to suppression of lnc13, which may cause gluten intolerance in people who were previously able to tolerate gluten.”
Photomicrograph showing the lnc13 RNA expression in an individual on a gluten-free diet. (Credit: Dr. Govind Bhagat, Department of Pathology and Cell Biology, Columbia University Medical Center)
This news release is also available in Spanish.
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This study was supported by grants from the National Institutes of Health (RO1-GM067005, R37-AI33443, RO1-AI093985, and R01-DK102180), the Basque
government (Spain), the Basque Department of Health (2011111034) and the Spanish Instituto de Salud Carlos III (PI10/00310).
The authors declare no financial or other conflicts of interest.
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The Celiac Disease Center at Columbia University Medical Center provides comprehensive medical care for adults and pediatric patients with celiac disease, including nutrition and attention to the multiple associated conditions that occur in celiac disease. The Center is involved in the care of thousands of patients with celiac disease and gluten sensitivity, providing better access to proper testing, diagnosis, treatment and follow-up care. Additional information is available online at celiacdiseasecenter.columbia.edu.
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