TLR 9 (rs352140) Gene Polymorphism in Helicobacter Pylori Infection

TLR 9 (rs352140) Gene Polymorphism in Helicobacter Pylori Infection in Children

study aimed to identify the role of TLR9 (rs352140) gene in suppressing or promoting the inflammation related to H. pylori infection in children.This cross-sectional study was conducted on 50 children with positive H. pylori infection and 50 age and sex matched, negative H. pylori children, all children undertook full history, complete clinical investigation, laboratory testing, upper digestive endoscopies and genotyping of TLR9 (rs352140).

Study Overview

• Status: Completed
• Conditions: H. Pylori Infection
• Intervention / Treatment: Diagnostic test: TLR TLR 9 (rs352140) gene polymorphism

Detailed Description

H. pylori infection is acknowledged as one of the major causes of gastrointestinal bacterial infections globally, imposing a substantial load on public health organizations, mostly in low-resource countries . H. pylori infection continues to pose a substantial challenge, particularly in vulnerable populations like infants, despite the significant advance made in health care organization and medicine .

The implications of H. pylori infection in minors have a profound impact on numerous aspects of health and well-being, which extend beyond the gastrointestinal tract.

In addition to its immediate effect on the gastric mucosa integrity of, H. pylori infection has systemic impacts that can have a negative impact on, growth trajectories, the nutritional status and overall health results of children who are affected .

A variety of gastrointestinal disorders, involving moderate gastritis and additional serious diseases like peptic ulcer disease, have been correlated with chronic infection by H. pylori. In addition, epidemiologic evidence indicates a potential correlation between an elevated hazard for acquiring gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma in later life and the acquisition of H. pylori infection during childhood. These long-term effects reinforce the urgent need to address H. pylori infection in children as a major community health importance .

Currently, there are numerous invasive and non-invasive diagnostic assessments accessible to identify H. pylori infection in children. However, tissue culture and the rapid urease test or concordant-positive histopathology tests remains the gold standard results .

Mast, macrophages, dendritic, eosinophils, neutrophils, and natural killer (NK) cells are cell actors of the innate immune system which provide antigen-independent defense against H. pylori infection .

Toll-like receptors (TLRs) are critical innate immunity regulators that can be stimulated upon the identifying of pathogen-associated molecular patterns (PAMPs) such as viral and bacterial ligands. They serve as the initial line of defense for the host against a variety of circumstances, involving H. pylori infection .

There are 13 TLRs (TLR1-13) in mammals, but only 10 (TLR1-10) are present in humans, but all are present in mice, with TLR10 being nonfunctional.

The human stomach's gastric epithelial cells are known to produce TLR4 and TLR9, which are crucial for innate immune signaling to H. pylori .

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt
    • Faculty of Medicine Benha University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. children with age between 1 and 18 years with gastrointestinal symptoms that necessitates upper digestive endoscopy like:

   • persistent pain in the abdomen and/or the stomach,
   • Heartburn,
   • vomiting,
   • nausea.

2. children who showed red flag signs like :

   • anemia,
   • gastrointestinal hemorrhage,
   • failure to thrive,
   • increased ESR .

Exclusion Criteria:

• cases on proton pump inhibitors,
• those with substantial medical diseases,
• those with gastrointestinal conditions that could explain their stomach discomfort (such as celiac disease, functional abdominal pain and inflammatory bowel disease).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: children with age between 1 and 18 years with gastrointestinal symptoms that necessitates upper dige; children with age between 1 and 18 years with gastrointestinal symptoms that necessitates upper digestive endoscopy like: persistent pain in the abdomen and/or the stomach, Heartburn, vomiting, and nausea. Additionally, children who showed red flag signs like anemia, gastrointestinal hemorrhage, failure to thrive, or increased ESR were as well involved.

Diagnostic test: TLR TLR 9 (rs352140) gene polymorphism; Genotyping of TLR9 (rs352140) was done using TaqMan mechanism on the Applied Biosystems™ 7500Fast Dx Real-Time PCR System (Applied Biosystems, Waltham, MA, United States) and a predesigned assay, namely C_2301954_20. A venous blood sample (2 mls) were withdrawn from each subject and were collected into sterile ethylene diaminetetra acetate "EDTA" (vacutainer) tube and were used for DNA extraction. DNA was extracted from fresh samples and stored at -20 °C till time of assay for determination of TLR9 (rs352140) polymorphism by using real time Polymerase chain reaction (rt PCR) technique. The blood samples were used for DNA extraction using the Gene JET Whole Blood Genomic DNA purification Mini Kit (Thermo Fisher Scientific, Germany) according to the manufacturer's protocol. Determination of DNA concentration was done using Nanodrop One spectrophotometer (thermoscientific, USA). A concentration of (1µg) from each sample was used for genotyping by rtPCR assay. Genotyping of TLR9 (rs352140)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TLR9 rs352140 gene polymorphism correlation with of H. pylori infection and incidence of gastritis in children	determination of TLR9 (rs352140) polymorphism by using real time Polymerase chain reaction (rt PCR) technique	in 1 to 3 months of complaint
TLR9 rs352140 gene polymorphism with abdominal pain , H. pylori infection and incidence of gastritis in children	determination of TLR9 (rs352140) polymorphism by using real time Polymerase chain reaction (rt PCR) technique	in 1 -3months of symptoms

Collaborators and Investigators

• Sponsor: Benha University

Publications and helpful links

General Publications

• Wicherska-Pawlowska K, Wrobel T, Rybka J. Toll-Like Receptors (TLRs), NOD-Like Receptors (NLRs), and RIG-I-Like Receptors (RLRs) in Innate Immunity. TLRs, NLRs, and RLRs Ligands as Immunotherapeutic Agents for Hematopoietic Diseases. Int J Mol Sci. 2021 Dec 13;22(24):13397. doi: 10.3390/ijms222413397.
• Elbehiry A, Marzouk E, Aldubaib M, Abalkhail A, Anagreyyah S, Anajirih N, Almuzaini AM, Rawway M, Alfadhel A, Draz A, Abu-Okail A. Helicobacter pylori Infection: Current Status and Future Prospects on Diagnostic, Therapeutic and Control Challenges. Antibiotics (Basel). 2023 Jan 17;12(2):191. doi: 10.3390/antibiotics12020191.
• Nguyen J, Kotilea K, Bontems P, Miendje Deyi VY. Helicobacter pylori Infections in Children. Antibiotics (Basel). 2023 Sep 12;12(9):1440. doi: 10.3390/antibiotics12091440.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2023
• Primary Completion (Actual): May 1, 2025
• Study Completion (Actual): September 1, 2025

Study Registration Dates

• First Submitted: November 25, 2025
• First Submitted That Met QC Criteria: December 4, 2025
• First Posted (Actual): December 17, 2025

Study Record Updates

• Last Update Posted (Actual): December 17, 2025
• Last Update Submitted That Met QC Criteria: December 4, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: TLR 9
• Additional Relevant MeSH Terms: Genetic Phenomena; Genetic Variation; Polymorphism, Genetic
• Other Study ID Numbers: MS-14-12-2022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No