Article: A functional single-nucleotide polymorphism in the promoter of the gene encoding interleukin 6 is associated with susceptibility to tuberculosis
| Title | A functional single-nucleotide polymorphism in the promoter of the gene encoding interleukin 6 is associated with susceptibility to tuberculosis |
|---|---|
| Authors | Zhang, G2 Zhou, B2 Wang, W2 4 Zhang, M2 Zhao, Y4 Wang, Z2 Yang, L2 Zhai, j2 Feng, CG3 Wang, JJ1 Chen, X2 |
| Issue Date | 2012 |
| Publisher | Oxford University Press. The Journal's web site is located at http://jid.oxfordjournals.org |
| Citation | Journal of Infectious Diseases, 2012, v. 205 n. 11, p. 1697-1704 [How to Cite?] DOI: http://dx.doi.org/10.1093/infdis/jis266 |
| 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. |
| ISSN | 0022-1899 2011 Impact Factor: 6.41 2011 SCImago Journal Rankings: 0.831 |
| DOI | http://dx.doi.org/10.1093/infdis/jis266 |
| PubMed Central ID | PMC3415858 |
| Grants | A Novel Hidden Markov Model to Predict microRNAs and their Targets Simultaneously and its Application to the Epstein-Barr virus |
| dc.contributor.author | Zhang, G | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| dc.contributor.author | Zhou, B | ||||||||||
| dc.contributor.author | Wang, W | ||||||||||
| dc.contributor.author | Zhang, M | ||||||||||
| dc.contributor.author | Zhao, Y | ||||||||||
| dc.contributor.author | Wang, Z | ||||||||||
| dc.contributor.author | Yang, L | ||||||||||
| dc.contributor.author | Zhai, j | ||||||||||
| dc.contributor.author | Feng, CG | ||||||||||
| dc.contributor.author | Wang, JJ | ||||||||||
| dc.contributor.author | Chen, X | ||||||||||
| dc.date.accessioned | 2012-05-30T03:56:53Z | ||||||||||
| dc.date.available | 2012-05-30T03:56:53Z | ||||||||||
| dc.date.issued | 2012 | ||||||||||
| dc.description.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. | ||||||||||
| dc.description.grant | A Novel Hidden Markov Model to Predict microRNAs and their Targets Simultaneously and its Application to the Epstein-Barr virus | ||||||||||
| dc.description.grantcode | 103716 | ||||||||||
| dc.description.nature | link_to_OA_fulltext | ||||||||||
| dc.identifier.citation | Journal of Infectious Diseases, 2012, v. 205 n. 11, p. 1697-1704 [How to Cite?] DOI: http://dx.doi.org/10.1093/infdis/jis266 | ||||||||||
| dc.identifier.doi | http://dx.doi.org/10.1093/infdis/jis266 | ||||||||||
| dc.identifier.epage | 1704 | ||||||||||
| dc.identifier.hkuros | 208296 | ||||||||||
| dc.identifier.isi | WOS:000304065600014
Funding Information: 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.). | ||||||||||
| dc.identifier.issn | 0022-1899 2011 Impact Factor: 6.41 2011 SCImago Journal Rankings: 0.831 | ||||||||||
| dc.identifier.issue | 11 | ||||||||||
| dc.identifier.pmcid | PMC3415858 | ||||||||||
| dc.identifier.pmid | 22457277 | ||||||||||
| dc.identifier.scopus | eid_2-s2.0-84861045821 | ||||||||||
| dc.identifier.spage | 1697 | ||||||||||
| dc.identifier.uri | http://hdl.handle.net/10722/148735 | ||||||||||
| dc.identifier.volume | 205 | ||||||||||
| dc.language | eng | ||||||||||
| dc.publisher | Oxford University Press. The Journal's web site is located at http://jid.oxfordjournals.org | ||||||||||
| dc.publisher.place | United States | ||||||||||
| dc.relation.ispartof | Journal of Infectious Diseases | ||||||||||
| dc.title | A functional single-nucleotide polymorphism in the promoter of the gene encoding interleukin 6 is associated with susceptibility to tuberculosis | ||||||||||
| dc.type | Article |
Author Affiliations
- The University of Hong Kong Li Ka Shing Faculty of Medicine
- Shenzhen People's Hospital
- National Institute of Allergy and Infectious Diseases
- South China Agricultural University

