Association of tumour necrosis factor-alpha (rs1800629 and rs361525) gene polymorphisms with tuberculosis susceptibility: a meta-analysis

Abstract Background Tuberculosis (TB) remains a significant global health challenge. Many complex factors contribute to the alarming statistics concerning TB. Among them are genetic factors, particularly polymorphisms in immune-related genes like tumor necrosis factor-alpha (TNF-alpha), which play a critical role in battling TB. The TNF-alpha gene polymorphisms have been extensively studied, and the results have remained inconsistent across populations. This meta-analysis focused on evaluating the association of these polymorphisms with TB risk based on more recent data. Methods A systematic literature search was conducted using PubMed, Google Scholar, and Science Direct to retrieve 9 relevant studies encompassing 2182 TB cases and 2329 controls on TNF-alpha polymorphisms and TB from 2018 to 2024. Case–control studies with adequate allele and genotype data were included, while previous meta-analyses, reviews and studies published before 2018 were excluded to minimize duplication. Statistical analyses were performed using MetaGenyo software. Results No significant association was found between TNF-308G/A (rs1800629) or TNF-238G/A (rs361525) polymorphisms and TB susceptibility across all genetic models, in both general and ethnic-specific analyses. However, the TNF-308G/A heterozygote model (GA vs. AA) showed a statistically significant protective effect in the American population (GA vs. AA, OR 0.30, 95% CI 0.10–0.85, p = 0.02). This finding suggests potential population-specific genetic influence. Further research should explore gene-environment and gene–gene interactions to clarify the complex role of TNF-alpha polymorphisms in TB susceptibility across diverse populations.