Genetic variations affecting a protein called T-bet may predispose individuals to inflammatory bowel disease (IBD), according to a study. This finding may contribute to the development of novel treatments for IBD and celiac disease.
The study, “Genetic Variants Alter T-Bet Binding and Gene Expression in Mucosal Inflammatory Disease,” appeared in the journal PLoS Genetics.
T-bet is a transcription factor or protein that regulates gene expression, which leads to protein production in cells. T-bet coordinates the body’s immune response and ensures production of certain immune system cells.
Previous research had suggested that changes known as single-nucleotide polymorphisms (SNPs) in the sequence of the gene encoding T-bet may interfere with gene expression, triggering inflammation. Now, researchers have found that patients with mucosal inflammatory diseases, Crohn’s disease, ulcerative colitis (UC) and celiac disease have a specific enrichment in polymorphisms that affect T-bet’s binding sites to DNA.
“We have found that IBD and celiac disease-associated [polymorphisms] are significantly enriched at T-bet binding sites,” researchers wrote. “Surprisingly, this association is not observed for [rheumatoid arthritis] or psoriasis, suggesting it may be specific for mucosal inflammatory disease.”
They also found that a polymorphism known as rs1465321 blocked the binding of T-bet to the IL18RAP gene, which was somewhat suppressed, predisposing individuals for celiac disease.
“Furthermore, we have identified genetic variants that alter T-bet binding to DNA, both in vitro and in vivo, including [the polymorphism] rs1465321, which we also identify as [a modifier] for IL18RAP and celiac disease,” according to the study. “Thus, these data provide a mechanistic explanation for why a single base change at this [protein] is associated with changes in gene expression and disease risk.”
Together, these findings support that T-bet proteins play an important role in the development of inflammatory conditions.
“Understanding how our DNA influences our risk of developing specific diseases is the key to developing precision therapies for the most severe illnesses,” Richard Jenner, one of the study’s co-senior authors, said in a news release. “While there is still a great deal of work to be done before this work results in new treatments for patients, it is a significant breakthrough.”