TY - JOUR
T1 - A functional single-nucleotide polymorphism in the promoter of the gene encoding interleukin 6 is associated with susceptibility to tuberculosis
AU - Zhang, Guoliang
AU - Zhou, Boping
AU - Wang, Wenfei
AU - Zhang, Mingxia
AU - Zhao, Yahua
AU - Wang, Zheng
AU - Yang, Lin
AU - Zhai, Jingnan
AU - Feng, Carl G.
AU - Wang, Junwen
AU - Chen, Xinchun
N1 - Funding Information:
Financial support. This work was supported by Eleven-Fifth Mega-Scientific Project on the “prevention and treatment of AIDS, viral hepatitis and other infectious diseases” (2008ZX10003-005), the Natural Science Foundation of China (grants 30872258 and 81172732), the Intramural Research Program, Department of Health and Human Services, National Institute of Allergy and Infectious Diseases, National Institutes of Health (to C. G. F.), and the Food and Health Bureau of Hong Kong (10091262 to J. W.). Potential conflicts of interest. All authors: No reported conflicts.
PY - 2012/6/1
Y1 - 2012/6/1
N2 - 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.MethodsGenotyping 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.ResultsThe 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.
AB - 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.MethodsGenotyping 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.ResultsThe 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.
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U2 - 10.1093/infdis/jis266
DO - 10.1093/infdis/jis266
M3 - Article
C2 - 22457277
AN - SCOPUS:84861045821
SN - 0022-1899
VL - 205
SP - 1697
EP - 1704
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 11
ER -