Yim J-J, Lee H W, Lee H S, Kim Y W, Han S K, Shim Y-S, Holland S M
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, and Lung Institute, Seoul National University College of Medicine, Chongno-Gu, Seoul, Republic of Korea.
Genes Immun. 2006 Mar;7(2):150-5. doi: 10.1038/sj.gene.6364274.
The observation that Toll-like receptor (TLR)2-deficient mice are highly susceptible to mycobacteria suggests that mutations altering TLR2 expression may impair host response to Mycobacterium tuberculosis. We evaluated the association between guanine-thymine (GT) repeat polymorphism in intron II of the TLR2 gene and the presence of tuberculosis (TB) in Koreans. The numbers of GT repeats were determined by PCR and gene scans for 176 TB patients and 196 controls. The recombinant TLR2 promoter/exonI/exonII/intronII/luciferase constructs including three representative repeats: (GT)13, (GT)20, and (GT)24 were transfected into K562 cells, and luciferase activities were estimated and compared. The expression of TLR2 on CD14+ peripheral blood mononuclear cells (PBMC) from healthy volunteers were measured with flow cytometry. Genotypes with shorter GT repeats were more common among TB patients (49.4 vs 37.7%, P=0.02). This observation was confirmed among 82 other TB patients as a validation cohort. Shorter GT repeats were associated with weaker promoter activities and lower TLR2 expression on CD14+ PBMCs. In conclusion, the development of TB disease in Koreans was associated with shorter GT repeats in intron II of the TLR2 gene. This association is correlated with lower expression of TLR2 through weaker promoter activity for genes with shorter GT repeats.
Toll样受体（TLR）2缺陷小鼠对分枝杆菌高度易感，这一观察结果表明，改变TLR2表达的突变可能会损害宿主对结核分枝杆菌的反应。我们评估了韩国人中TLR2基因内含子II中鸟嘌呤-胸腺嘧啶（GT）重复多态性与结核病（TB）存在之间的关联。通过聚合酶链反应（PCR）和基因扫描确定了176例结核病患者和196例对照的GT重复数。将包含三个代表性重复序列：（GT）13、（GT）20和（GT）24的重组TLR2启动子/外显子I/外显子II/内含子II/荧光素酶构建体转染到K562细胞中，并估计和比较荧光素酶活性。用流式细胞术检测健康志愿者CD14+外周血单核细胞（PBMC）上TLR2的表达。GT重复较短的基因型在结核病患者中更为常见（49.4%对37.7%，P=0.02）。在另外82例结核病患者作为验证队列中证实了这一观察结果。较短的GT重复与较弱的启动子活性以及CD14+PBMC上较低的TLR2表达相关。总之，韩国人结核病的发生与TLR2基因内含子II中较短的GT重复有关。这种关联与GT重复较短的基因启动子活性较弱导致TLR2表达较低相关。
