A Study on the Associations of Toll-like Receptor 5 Gene Polymorphisms With Crohn's Disease in Chinese Patients

Crohn's Disease, Polymorphism, Single Nucleotide, Toll-like Receptor 5, Ustekinumab

The exact etiology and pathogenesis of Crohn's disease (CD) have not been fully elucidated, and may be related to the combined effects of genetics, environment, immunity, gut microbiota, and many other factors. Toll like receptor 5 (TLR5) is one of the transmembrane pattern recognition receptors that specifically recognizes and binds to bacterial flagellar proteins, activating the nuclear factor kappa-B (NF - κ B) signaling pathway and triggering immune and inflammatory responses. The TLR5 gene is located in the 1q33.3 region of the human chromosome, with a total length of approximately 34kb and 6 exons. Research data from European populations shows that two single nucleotide polymorphisms, rs5744168 and rs5744174, in the TLR5 gene may be closely associated with the risk of developing CD. According to Danish scholars, the mutation of rs5744174 may affect the clinical response of CD patients treated with anti-tumor necrosis factor - α (TNF - α) drugs. Ustekinumab (UST) is a fully humanized monoclonal antibody against the p40 subunit and is one of the commonly used biologics for treating CD patients. The p40 subunit is a common component of interleukin-12 (IL) and IL-23, therefore UST can simultaneously inhibit the IL-12 and IL-23 signaling pathways, exerting anti-inflammatory effects by suppressing immune cell differentiation such as T helper cell 1 (Th1), Th17 cells, natural killer cells, macrophages, etc. Among CD patients receiving UST treatment, it was found that patients who achieved clinical response in the early stage were more likely to achieve clinical remission in the middle and later stages compared to those who did not , indicating that evaluating early response has certain clinical value in predicting the efficacy of UST in the middle and later stages. This study aims to explore the relationship between TLR5 (rs5744168 and rs5744174) gene polymorphism and the risk and clinical pathological characteristics of CD in the Han population of Zhejiang, and analyze whether TLR5 gene mutations affect the early response of UST treatment for CD patients. The aim is to provide some clues and basis for revealing the genetic and immunological pathogenesis of CD and developing precise individualized treatment plans for UST.

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