TLR2 variants and Helicobacter pylori: revisiting a controversial link

Although polymorphisms in the Toll-like receptor 2 (TLR2) gene have been proposed as host genetic factors influencing susceptibility to Helicobacter pylori infection, existing data remain inconclusive. This meta-analysis aimed to clarify whether two common variants - rs3804099 and del -196 to -174 - contribute to infection risk across diverse populations.

A systematic search of PubMed, Scopus, and Web of Science (up to January 2025) identified eligible case-control studies examining the association between TLR2 polymorphisms and H. pylori infection. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models. Heterogeneity, publication bias, and sensitivity were assessed according to PRISMA 2020 guidelines.

Ten studies comprising 4,521 subjects were included. Pooled analyses under allelic, dominant, recessive, homozygous, and heterozygous models revealed no significant association between either rs3804099 or del -196 to -174 polymorphisms and infection risk. Substantial inter-study heterogeneity was observed, particularly for rs3804099, but sensitivity analyses confirmed the stability of pooled results.

This meta-analysis refutes a consistent genetic association between TLR2 rs3804099 or del -196 to -174 polymorphisms and H. pylori infection. The findings suggest that host innate immunity variability alone does not explain differences in infection susceptibility among populations. Future studies integrating bacterial virulence genotypes and host immunogenetic profiles are warranted to delineate population-specific risk mechanisms.