Abstract
Abstract Background. Genetic variation influences susceptibility or resistance to tuberculosis (TB). Interleukin-6 contributes to protection against TB in mice, however, its role in regulating susceptibility or resistance to TB in humans is unclear. Methods. Genotyping of polymorphisms in IL-6 and IL-6R (CD126) genes were performed in two independent cohorts, namely experimental (495 cases and 358 controls) and validation (1383 cases and 1149 controls) populations. The associations of the variants with tuberculosis were tested using two case-control association studies. In addition, the regulatory effects of SNP rs1800796 (-572C>G) on IL-6 production in plasma and CD14+ monocyte cultures stimulated with a Mycobacterium tuberculosis (Mtb) product were assessed. Results. The rs1800796 polymorphism is associated with increased resistance to TB (odds ratio, 0.771; confidential interval 0.684-0.870). The rs1800796GG genotype is strongly associated with reduced risk to TB (odds ratio, 0.621; confidential interval 0.460-0.838). Interestingly, CD14+ monocytes isolated from individuals with rs1800796GG genotype produced significantly lower IL-6 in response to Mtb 19kDa lipoprotein than those with CC or CG genotype do. Conclusions. We identified a genetic polymorphism in IL-6 promoter that regulates the cytokine production and host resistance to pulmonary TB in Chinese population.
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