Changes in T-bet Proteins May Predispose Individuals For IBD, Study Says

Changes in T-bet Proteins May Predispose Individuals For IBD, Study Says
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
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