Effects of the STING R232/H232 Variant on the Prognosis of Inflammatory Bowel Disease

Abstract

Aim: Inflammatory bowel disease (IBD) refers to a group of diseases which cause chronic and recurrent inflammation in different parts of the digestive tract, such as Crohn’s disease (CD) or ulcerative colitis (UC). CD can affect both the large and small intestines, while UC usually affects only the large intestine. Recent studies in immunogenetics have revealed that the innate immune system is crucial in triggering gut inflammation, and rare variants in genes which function in this system are important risk factors for this disease. Stimulator of interferon genes (STING) is a nucleotide-binding endoplasmic reticulum protein involved in the innate immune response. This study aimed to analyse the R232/H232 variant in the STING1 gene in pediatric patients diagnosed with IBD and to investigate whether this variant is associated with the prognosis of IBD. Materials and Methods: Thirty-five pediatric patients admitted with a prediagnosis of IBD were included in this study. The R232/H232 variant was determined by end-point genotyping analysis after real-time reverse transcription-polymerase chain reaction (qRT-PCR) reactions using affinity probes. qRT-PCR analyses were performed to determine the mRNA expression levels of STING and interferon-induced genes in tissue samples. The western blotting method determined STING expression at the protein level. Results: It was determined that 31.43% of the patients had heterozygous (R232/H232), and 68.57% had homozygous (H232/H232) genotypes. A significant difference was found between the genotype distribution and treatment stage. It was determined that 87.50% of the patients who started second-stage treatment had homozygous genotypes. It was also found that homozygous patients had longer durations of attacks than heterozygous patients. Conclusion: R232/H232, the most common variant in the STING1 gene, affects treatment response and attack duration in patients with IBD. Therefore, we suggest that variants in the STING1 gene may be used to develop genetic-based personalized treatment strategies for IBD patients in the future.

Keywords

• sting
• r232/h232
• inflammatory bowel disease
• crohn’s disease
• ulcerative colitis