A Functional Single-Nucleotide Polymorphism in the Promoter of the Gene Encoding Interleukin 6 Is Associated With Susceptibility to Tuberculosis
A Functional Single-Nucleotide Polymorphism in the Promoter of the Gene Encoding Interleukin 6 Is Associated With Susceptibility to Tuberculosis
复制标题
编码白细胞介素6的基因启动子中的功能性单核苷酸多态性与结核病易感性相关。
DOI：
10.1093/infdis/jis266
复制
发表时间：
2012-06-01
影响因子：
6.4
通讯作者：
Chen, Xinchun
中科院分区：
文献类型：
--
作者：
Zhang, Guoliang;Zhou, Boping;Chen, Xinchun
背景
基因变异会影响结核病的易感性或抗药性。白介素6(IL-6)对小鼠的结核病有保护作用。然而，它在调节人类对结核病的易感性或耐药性方面的作用尚不清楚。
方法
对两个独立的队列、一个实验人群(495例和358名对照)和一个验证人群(1383例和1149名对照)进行了IL-6和IL-6R(CD126)基因多态性的基因分型。通过2项病例对照关联研究检验了这些变异与结核病的相关性。此外，我们还研究了单核苷酸多态rs1800796(-572C>；G)对结核分枝杆菌产物刺激的血浆和CD14(+)单核细胞产生IL-6的调节作用。
结果
Rs1800796多态与结核病耐药性增加相关(优势比[OR]，0.771；95%可信区间，.684-.870)。Rs1800796GG基因与结核病风险降低密切相关(OR，0.621；95%CI，.460-.838)。有趣的是，携带rs1800796GG基因的个体分离的CD14(+)单核细胞对结核分枝杆菌19-kDa脂蛋白的反应产生的IL-6显著低于携带CC或CG基因的个体。
结论
我们在IL-6启动子中发现了一种基因多态性，它调节中国人群中细胞因子的产生和宿主对肺结核的抵抗力。
BACKGROUND
Genetic variation influences susceptibility or resistance to tuberculosis. Interleukin 6 (IL-6) contributes to protection against tuberculosis in mice. However, its role in regulating susceptibility or resistance to tuberculosis in humans is unclear.
METHODS
Genotyping of polymorphisms in IL-6 and IL-6R (CD126) genes was performed in 2 independent cohorts, an experimental population (495 cases and 358 controls) and a validation population (1383 cases and 1149 controls). The associations of the variants with tuberculosis were tested using 2 case-control association studies. In addition, the regulatory effects of single-nucleotide polymorphism rs1800796 (-572C > G) on IL-6 production in plasma and CD14(+) monocyte cultures stimulated with a Mycobacterium tuberculosis (M. tuberculosis) product were assessed.
RESULTS
The rs1800796 polymorphism is associated with increased resistance to tuberculosis (odds ratio [OR], 0.771; 95% confidential interval, .684-.870). The rs1800796GG genotype is strongly associated with reduced risk to tuberculosis (OR, 0.621; 95% CI, .460-.838). Interestingly, CD14(+) monocytes isolated from individuals with rs1800796GG genotype produced significantly less IL-6 in response to M. tuberculosis 19-kDa lipoprotein than those with CC or CG genotype.
CONCLUSIONS
We identified a genetic polymorphism in the IL-6 promoter that regulates cytokine production and host resistance to pulmonary tuberculosis in Chinese populations.