The Role of Toll-like Receptor 2 Polymorphisms in Susceptibility to and Severity of Tuberculosis: A Systematic Review

Pulmonary tuberculosis (TB) remains a global health threat, with individual genetic determinants like Toll-like receptor 2 (TLR2) gene variations potentially modulating immune responses to Mycobacterium tuberculosis. This systematic review evaluates the role of TLR2 polymorphisms in influencing susceptibility to and clinical manifestations of pulmonary TB. Following PRISMA guidelines, a comprehensive search of PubMed, Scopus, and ScienceDirect was conducted through July 2024 for observational studies investigating TLR2 single-nucleotide polymorphisms (SNPs) and active TB. Risk of bias was assessed using the Newcastle-Ottawa Scale. Of 8878 identified articles, 32 studies met the inclusion criteria. The most frequently investigated variants, Arg753Gln (rs5743708), -196 to -174 del, and rs3804099, were consistently associated with increased TB susceptibility, particularly in Asian and African populations. Furthermore, specific polymorphisms correlated with greater disease severity, including cavitary lesions and aggressive clinical progression. In conclusion, TLR2 genetic polymorphisms significantly increase the risk of developing pulmonary TB and contribute to more severe clinical outcomes. These findings emphasize the potential of genetic profiling in enhancing TB control strategies and developing personalized diagnostic or therapeutic approaches.