Effects of STING gene variants on the prognosis of inflammatory bowel disease
Project no. 25244 · Status: Kapanmış (Yayın bekleniyor) · 2022
Summary
<p>cGAS and STING, which act as cytoplasmic DNA sensors, are key regulatory proteins that trigger the innate immune response. After their activation, the signal is transmitted to the nucleus via TBK1 and IRF3 proteins, initiating the transcription of type I interferon and interferon-stimulated genes that regulate many innate and adaptive immune system cells. Although the primary function of cGAS/STING is to protect the organism against pathogen attacks, irregularities in this pathway can trigger the pathological interferon response that underlies many diseases. Studies have shown that excessive activation of cGAS-STING may contribute to the disruption of gastrointestinal homeostasis and suggest that the cGAS/STING pathway may be a promising therapeutic target. Inflammatory Bowel Disease (IBD) refers to a group of diseases, such as Crohn's disease (CD) and Ulcerative Colitis (UC), that cause chronic and recurrent inflammation in different parts of the digestive system. These diseases, whose prevalence is rapidly increasing worldwide, affect people of all ages and all aspects of life. Although the etiology is not fully known, it is reported that genetic and environmental factors play important roles in the development of IBD. Our aim in this study is to analyze 3 gene variants of the STING gene, named as HAQ (R71H-G230A-R293Q), in pediatric cases diagnosed with IBD and to determine the effects of these variants on cGAS/STING activation in the intestinal endothelium and IBD pathophysiology. Within the scope of the project, it was planned to collect blood and biopsy samples from IBD cases, perform variant analyses, and compare cGAS/STING activation in biopsy samples by analyzing them in cases with R71/H71, G230/A230 and R293/Q293 genotypes.</p>