Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China.
Health Management Center, West China Hospital, Sichuan University, Chengdu, China.
Front Immunol. 2021 May 24;12:660384. doi: 10.3389/fimmu.2021.660384. eCollection 2021.
Nuclear transcription factor erythroid 2 p45-related factor 2 (Nrf2), encoded by , functions as a key transcription factor and regulates expression of antioxidant genes. Our study aimed to investigate the association of single nucleotide polymorphisms of with tuberculosis (TB) and latent tuberculosis infection (LTBI) and the underlying causal mechanisms.
1950 unrelated Chinese Han participants were included in our two independent study groups. Five tag polymorphisms were selected and genotyped. The functional effects of the rs13005431 polymorphism were confirmed by dual-luciferase reporter assays and mRNA level comparisons.
Rs13005431_C and rs2364723_G were associated with increased TB susceptibility ( = 0.010 and = 0.041) after adjustment for confounding factors. rs6726395_A was associated with increased risk of active TB (=0.035) in a comparison with the LTBI group. The frequency of haplotype rs1049751- rs13005431 AC was higher in the TB group ( =0.013), while frequency of haplotype AT was higher in the healthy control group ( =0.025). The luciferase activity of a plasmid with the rs13005431C-promoter was significantly lower than that of the rs13005431T-promoter. In addition, neutrophils with the CC/TC genotypes which were activated by GM-CSF showed a decreased level of mRNA when compared with the rs13005431 TT genotype.
Our study suggests that allele C of rs13005431 might increase the susceptibility to TB by down-regulating the transcriptional activity of .
核转录因子红细胞 2 相关因子 2（Nrf2），由 编码，作为关键转录因子发挥作用，调节抗氧化基因的表达。我们的研究旨在探讨单核苷酸多态性与结核病（TB）和潜伏性结核感染（LTBI）的关联及其潜在的因果机制。
我们纳入了两个独立的中国汉族研究组的 1950 名无关个体。选择并对 5 个标签多态性进行了基因分型。通过双荧光素酶报告基因检测和 mRNA 水平比较来验证 rs13005431 多态性的功能效应。
在调整混杂因素后，rs13005431_C 和 rs2364723_G 与 TB 易感性增加相关（ = 0.010 和 = 0.041）。与 LTBI 组相比，rs6726395_A 与活动性 TB 风险增加相关（ = 0.035）。与 TB 组相比，rs1049751-rs13005431 AC 单倍型的频率更高（ = 0.013），而 AT 单倍型的频率在健康对照组中更高（ = 0.025）。携带 rs13005431C-启动子的质粒的荧光素酶活性明显低于携带 rs13005431T-启动子的质粒。此外，GM-CSF 激活的 CC/TC 基因型的中性粒细胞与 rs13005431 TT 基因型相比， mRNA 水平降低。
我们的研究表明，rs13005431 的等位基因 C 可能通过下调 的转录活性增加 TB 的易感性。
