Polymorphisms in genes that control immune function and regulation may influence susceptibility to pulmonary tuberculosis (TB). In this study, 14 polymorphisms in 12 key genes involved in the immune response (VDR, MR1, TLR1, TLR2, TLR10, SLC11A1, IL1B, IL10, IFNG, TNF, IRAK1, and FOXP3) were tested for their association with pulmonary TB in 271 patients with TB and 251 community-matched controls from the Republic of Moldova. In addition, gene–gene interactions involved in TB susceptibility were analyzed for a total of 43 genetic loci. Single nucleotide polymorphism (SNP) analysis revealed a nominal association between TNF rs1800629 and pulmonary TB (Fisher exact test P = 0.01843). In the pairwise interaction analysis, the combination of the genotypes TLR6 rs5743810 GA and TLR10 rs11096957 GT was significantly associated with an increased genetic risk of pulmonary TB (OR = 2.48, 95% CI = 1.62–3.85; Fisher exact test P value = 1.5 × 10⁻⁵, significant after Bonferroni correction). In conclusion, the TLR6 rs5743810 and TLR10 rs11096957 two-locus interaction confers a significantly higher risk for pulmonary TB; due to its high frequency in the population, this SNP combination may serve as a novel biomarker for predicting TB susceptibility.

控制免疫功能和调节的基因中的多态性可能会影响对肺结核 (TB) 的易感性。在这项研究中，涉及免疫反应的 12 个关键基因（VDR、MR1、TLR1、TLR2、TLR10、SLC11A1、IL1B、IL10、IFNG、TNF、IRAK1和FOXP3 ）的 14 个多态性) 在摩尔多瓦共和国的 271 名结核病患者和 251 名社区匹配的对照中测试了它们与肺结核的关联。此外，共分析了 43 个基因位点中涉及 TB 易感性的基因-基因相互作用。单核苷酸多态性 (SNP) 分析揭示了TNF rs1800629 与肺结核之间的名义关联（Fisher 精确检验P  = 0.01843）。在成对相互作用分析中，基因型TLR6 rs5743810 GA 和TLR10 rs11096957 GT 的组合与肺结核的遗传风险增加显着相关（OR = 2.48, 95% CI = 1.62-3.85；Fisher 精确检验P值 = 1.5 × 10 ^-5，在 Bonferroni 校正后显着）。总之，TLR6 rs5743810 和TLR10 rs11096957 两个位点相互作用会显着增加患肺结核的风险；由于其在人群中的高频率，这种 SNP 组合可以作为预测结核病易感性的新型生物标志物。