Association Between Functional Nucleotide Polymorphisms Up-regulating Transforming Growth Factor β1 Expression and Increased Tuberculosis Susceptibility.
Association Between Functional Nucleotide Polymorphisms Up-regulating Transforming Growth Factor β1 Expression and Increased Tuberculosis Susceptibility.
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功能性核苷酸多态性上调转化生长因子β1 表达与结核病易感性增加之间的关联
DOI：
10.1093/infdis/jiaa585
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发表时间：
2022-03-02
期刊：
影响因子：
--
通讯作者：
Zhang G
中科院分区：
文献类型：
--
作者：
Zhang S;Li G;Bi J;Guo Q;Fu X;Wang W;Liu S;Xiao G;Ou M;Zhang J;He X;Li F;Li G;Feng CG;Chen X;Zhang G
既往研究表明，转化生长因子β1（transforming growth factor β 1，TGT β1）在临床结核病中具有免疫抑制作用。然而，TGF-β1基因多态性对人类结核病易感性的贡献仍不确定。在这项研究中，我们发现TGF-β1基因的单核苷酸多态性（SNPs）与发现队列中结核病易感性的增加有关（1533例病例患者和1445例对照）和验证队列（832例病例组和1084例对照组），2个位于启动子区的SNPs（rs 2317130和rs 4803457）处于强连锁不平衡状态。SNP rs 2317130与结核病的严重程度相关。进一步的研究表明rs 2317130 CC基因型与TGF-β1和IL-17 A的产生有关。rs 2317130 C等位基因可能通过调节TGF-β1启动子与细胞核提取物的结合活性而影响TGF-β1启动子的活性。这些发现为了解TGF-β1在人类结核病中的致病作用提供了新的见解，并揭示了TGF-β1启动子SNP在结核分枝杆菌感染期间调节免疫反应的功能。rs 2317130 CC基因型功能性单核苷酸多态性上调结核分枝杆菌特异性转化生长因子β1和白细胞介素17 A表达与结核病易感性增加相关
Previous studies demonstrated that transforming growth factor (TGT) β1 plays an immunosuppressive role in clinical tuberculosis. However, the contribution of TGF-β1 gene polymorphisms to human tuberculosis susceptibility remains undetermined. In this study, we showed that single-nucleotide polymorphisms (SNPs) in TGF-β1 gene were associated with increased susceptibility to tuberculosis in the discovery cohort (1533 case patients and 1445 controls) and the validation cohort (832 case patients and 1084 controls), and 2 SNPs located in the promoter region (rs2317130 and rs4803457) are in strong linkage disequilibrium. The SNP rs2317130 was associated with the severity of tuberculosis. Further investigation demonstrated that rs2317130 CC genotype is associated with higher TGF-β1 and interleukin 17A production. The mechanistic study showed that rs2317130 C allele affected TGF-β1 promoter activity by regulating binding activity to nuclear extracts. These findings provide insights into the pathogenic role of TGF-β1 in human tuberculosis and reveal a function for the TGF-β1 promoter SNPs in regulating immune responses during Mycobacterium tuberculosis infection. Functional single-nucleotide polymorphism of rs2317130 CC genotype, up-regulating Mycobacterium tuberculosis–specific transforming growth factor β1 and interleukin 17A expression, is associated with increased tuberculosis susceptibility.
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影响因子：
14.2
作者：
Hoshino, H;Laan, M;Lindén, A
通讯作者：
Lindén, A
影响因子：
2.3
作者：
Abraham, Selvajothi;Sweet, Thersa;Amini, Shohreh
通讯作者：
Amini, Shohreh
影响因子：
4.4
作者：
Cruz, Miguel;Manuel Fragoso, Jose;Vargas-Alarcon, Gilberto
通讯作者：
Vargas-Alarcon, Gilberto
TGFβ 信号的背景
DOI：
10.1038/nrm3434
发表时间：
2012-10
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
5.5
作者：
Jurado, Javier O.;Pasquinelli, Virginia;Garcia, Veronica E.
通讯作者：
Garcia, Veronica E.