A functional single-nucleotide polymorphism in the promoter of the gene encoding interleukin 6 is associated with susceptibility to tuberculosis

Guoliang Zhang, Boping Zhou, Wenfei Wang, Mingxia Zhang, Yahua Zhao, Zheng Wang, Lin Yang, Jingnan Zhai, Carl G. Feng, Junwen Wang, Xinchun Chen

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1697-1704
Number of pages8
JournalJournal of Infectious Diseases
Volume205
Issue number11
DOIs
StatePublished - Jun 1 2012
Externally publishedYes

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Single Nucleotide Polymorphism
Interleukin-6
Tuberculosis
Genes
Genotype
Mycobacterium tuberculosis
Monocytes
Odds Ratio
Population
Genetic Polymorphisms
Pulmonary Tuberculosis
Lipoproteins
Case-Control Studies
Cytokines

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

Cite this

A functional single-nucleotide polymorphism in the promoter of the gene encoding interleukin 6 is associated with susceptibility to tuberculosis. / Zhang, Guoliang; Zhou, Boping; Wang, Wenfei; Zhang, Mingxia; Zhao, Yahua; Wang, Zheng; Yang, Lin; Zhai, Jingnan; Feng, Carl G.; Wang, Junwen; Chen, Xinchun.

In: Journal of Infectious Diseases, Vol. 205, No. 11, 01.06.2012, p. 1697-1704.

Research output: Contribution to journalArticle

Zhang, Guoliang ; Zhou, Boping ; Wang, Wenfei ; Zhang, Mingxia ; Zhao, Yahua ; Wang, Zheng ; Yang, Lin ; Zhai, Jingnan ; Feng, Carl G. ; Wang, Junwen ; Chen, Xinchun. / A functional single-nucleotide polymorphism in the promoter of the gene encoding interleukin 6 is associated with susceptibility to tuberculosis. In: Journal of Infectious Diseases. 2012 ; Vol. 205, No. 11. pp. 1697-1704.
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abstract = "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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T1 - A functional single-nucleotide polymorphism in the promoter of the gene encoding interleukin 6 is associated with susceptibility to tuberculosis

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AU - Zhao, Yahua

AU - Wang, Zheng

AU - Yang, Lin

AU - Zhai, Jingnan

AU - Feng, Carl G.

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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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