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

Helicobacter pylori (H. pylori) contamination is a significant reason of the chronic gastric inflammation also is related to numerous gastrointestinal diseases, including peptic ulcers, chronic gastritis, mucosa-associated lymphoid tissue (MALT) lymphoma, , gastric atrophy, and gastric cancer (GC). Bacterium disrupts the gastric mucosal homeostasis primarily through inflammatory cytokines and its virulence factor, cytotoxin-associated gene pathogenicity island (Cag PAI). Cag PAI encodes a type IV secretion system (T4SS) that introduces CagA protein into the host cells, thereby initiating pro-inflammatory signaling cascades. Initiating the host's immune response to H. pylori and recognizing pathogen-associated molecular patterns (PAMPs) are critical functions of toll-like receptors (TLRs), particularly TLR4, TLR2, TLR5, and TLR9. Among these, TLR9 is considered as an intracellular receptor that notices unmethylated CpG motifs in bacterial DNA, contributing to immune surveillance and mucosal healing. Interestingly, while TLR activation generally promotes inflammation and oncogenic pathways via MAPKs and prostaglandin E2, TLR9 also has anti-inflammatory effects that help maintain mucosal integrity. The current review focuses on the genetic polymorphism TLR9 (rs352140) and its influence on inflammation in pediatric H. pylori infections. This single nucleotide polymorphism (SNP) may modulate TLR9 expression or function, thereby impacting host’s inflammatory response. It is imperative to comprehend the function of TLR9 variants, particularly rs352140, to evaluate the individual sensitivity to H. pylori-induced gastric pathology in kids. As only from 1% to 2% of infected cases acquire GC, genetic factors such as TLR9 polymorphisms may elucidate differential disease outcomes and could potentially serve as biomarkers for risk stratification and targeted therapy.