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

NCT ID: NCT07035678

Last Updated: 2025-06-25

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 825 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-01-01
• Study Completion Date: 2025-05-01

Brief Summary

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.

Conditions

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

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: RETROSPECTIVE

Study Groups

Crohn's disease group

Diagnosed with Crohn's disease.

No interventions assigned to this group

Normal control group

Healthy individuals without a history of rheumatoid arthritis, systemic lupus erythematosus, intestinal tuberculosis, ischemic enteritis, radiation enteritis, tumors, etc.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

1. After receiving IFX conventional treatment plan for 30 weeks;

2. Not participated in any other experimental projects in the past three months;

3. There are no other serious and life-threatening diseases in various systems.

Exclusion Criteria

1. Pregnancy;

2. Breastfeeding;

3. Severe drug allergy (having experienced severe drug allergic reactions such as anaphylactic shock, systemic dermatitis, etc.);

4. Merge with other autoimmune diseases (such as systemic lupus erythematosus, rheumatoid arthritis, autoimmune thyroiditis);

5. Merge malignant tumors;

6. Serious cardiovascular and cerebrovascular diseases;

7. Poor patient compliance or presence of mental disorders;

8. Incomplete case data.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Second Affiliated Hospital of Wenzhou Medical University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Second Affiliated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, China

Countries

China

Other Identifiers

SAHoWMU-CR2025-01-221

Identifier Type: -

Identifier Source: org_study_id