title: A functional single-nucleotide polymorphism in the promoter of the gene encoding interleukin 6 is associated with susceptibility to tuberculosis.
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.
  
  
  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.
authors.affiliation: Shenzhen Third People's Hospital, Guangdong Medical College, China.
authors.forename: Guoliang
authors.initials: G
authors.lastname: Zhang
authors.forename: Boping
authors.initials: B
authors.lastname: Zhou
authors.forename: Wenfei
authors.initials: W
authors.lastname: Wang
authors.forename: Mingxia
authors.initials: M
authors.lastname: Zhang
authors.forename: Yahua
authors.initials: Y
authors.lastname: Zhao
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.forename: Jingnan
authors.initials: J
authors.lastname: Zhai
authors.forename: Carl G
authors.initials: CG
authors.lastname: Feng
authors.forename: Junwen
authors.initials: J
authors.lastname: Wang
authors.forename: Xinchun
authors.initials: X
authors.lastname: Chen
mesh_terms: D000328:Adult; D002681:China; D015331:Cohort Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D019947:Receptors, Interleukin-6 / Q000235:genetics; D014376:Tuberculosis / Q000235:genetics*
chemical_list: D015850:Interleukin-6; D019947:Receptors, Interleukin-6