Skip to main content
SpringerLink
Log in

Association of genetic polymorphisms in the IL12-IFNG pathway with susceptibility to and prognosis of pulmonary tuberculosis in a Chinese population

  • Brief Report
  • Published:
European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

Abstract

Cytokines are crucial in activation of the cell-mediated immunity required for eliminating pathogens and controlling intracellular growth of Mycobacterium tuberculosis (TB). Genetic variants in the IL12-IFNG axis are hypothesized to be involved in the development and progression of TB. Genetic polymorphisms of rs2243115 and rs568408 in IL12A, rs3212227 in IL12B and rs2430561 in IFNG(+874) were detected in 522 pulmonary TB cases and 527 controls recruited from Yangzhong and Wujin County of China. It was found that genetic variants TG/GG of rs2243115(IL12A) were associated with a decreased risk of TB, with odds ratio (95% confidence interval) of 0.70 (0.49–0.99), whereas variant genotypes AT/TT of rs2430561(IFNG) conferred 82% less risk for treatment failure, with a hazard ratio of 0.18 (95% confidence interval 0.04–0.73). Cumulative effects analysis revealed that the risk of TB increased significantly with the number of unfavorable genotypes in IL12 genes. Furthermore, MDR analysis showed potential higher-order gene–gene and gene–environment interactions and indicated different outcomes based on distinct genotype profiles. Results from this study demonstrate that genetic polymorphisms of the IL12-IFNG pathway may individually or jointly contribute to the susceptibility to and prognosis of pulmonary TB.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

References

  1. Young DB, Perkins MD, Duncan K, Barry CE 3rd (2008) Confronting the scientific obstacles to global control of tuberculosis. J Clin Invest 118(4):1255–1265

    Article  CAS  PubMed  Google Scholar 

  2. Bellamy R (2003) Susceptibility to mycobacterial infections: the importance of host genetics. Genes Immun 4(1):4–11

    Article  CAS  PubMed  Google Scholar 

  3. Korbel DS, Schneider BE, Schaible UE (2008) Innate immunity in tuberculosis: myths and truth. Microbes Infect 10(9):995–1004

    Article  CAS  PubMed  Google Scholar 

  4. van de Vosse E, Hoeve MA, Ottenhoff TH (2004) Human genetics of intracellular infectious diseases: molecular and cellular immunity against mycobacteria and salmonellae. Lancet Infect Dis 4(12):739–749

    Article  PubMed  Google Scholar 

  5. Selvaraj P, Alagarasu K, Harishankar M, Vidyarani M, Nisha Rajeswari D, Narayanan PR (2008) Cytokine gene polymorphisms and cytokine levels in pulmonary tuberculosis. Cytokine 43(1):26–33

    Article  CAS  PubMed  Google Scholar 

  6. Mendez-Samperio P (2010) Role of interleukin-12 family cytokines in the cellular response to mycobacterial disease. Int J Infect Dis 14(5):e366–e371

    Article  PubMed  Google Scholar 

  7. Wakeham J, Wang J, Magram J, Croitoru K, Harkness R, Dunn P, Zganiacz A, Xing Z (1998) Lack of both types 1 and 2 cytokines, tissue inflammatory responses, and immune protection during pulmonary infection by Mycobacterium bovis bacille Calmette-Guerin in IL-12-deficient mice. J Immunol 160(12):6101–6111

    CAS  PubMed  Google Scholar 

  8. Cooper AM, Magram J, Ferrante J, Orme IM (1997) Interleukin 12 (IL-12) is crucial to the development of protective immunity in mice intravenously infected with Mycobacterium tuberculosis. J Exp Med 186(1):39–45

    Article  CAS  PubMed  Google Scholar 

  9. Cooper AM, Khader SA (2008) The role of cytokines in the initiation, expansion, and control of cellular immunity to tuberculosis. Immunol Rev 226:191–204

    Article  CAS  PubMed  Google Scholar 

  10. Condos R, Rom WN, Liu YM, Schluger NW (1998) Local immune responses correlate with presentation and outcome in tuberculosis. Am J Respir Crit Care Med 157(3 Pt 1):729–735

    CAS  PubMed  Google Scholar 

  11. Peng JC, Abu Bakar S, Richardson MM, Jonsson JJ, Frazer IH, Nielsen LK, Morahan G, Thomas R (2006) IL10 and IL12B polymorphisms each influence IL-12p70 secretion by dendritic cells in response to LPS. Immunol Cell Biol 84(2):227–232

    Article  CAS  PubMed  Google Scholar 

  12. Wang J, Shen H (2009) Review of cigarette smoking and tuberculosis in China: intervention is needed for smoking cessation among tuberculosis patients. BMC Public Health 9:292

    Article  PubMed  Google Scholar 

  13. Pravica V, Perrey C, Stevens A, Lee JH, Hutchinson IV (2000) A single nucleotide polymorphism in the first intron of the human IFN-gamma gene: absolute correlation with a polymorphic CA microsatellite marker of high IFN-gamma production. Hum Immunol 61(9):863–866

    Article  CAS  PubMed  Google Scholar 

  14. Matsui M (2007) Roles of the novel interleukin-12-associated cytokine, interleukin-23, in the regulation of T-cell-mediated immunity. Hepatol Res 37(Suppl 3):S310–S318

    Article  CAS  PubMed  Google Scholar 

  15. Filipe-Santos O, Bustamante J, Chapgier A, Vogt G, de Beaucoudrey L, Feinberg J, Jouanguy E, Boisson-Dupuis S, Fieschi C, Picard C, Casanova JL (2006) Inborn errors of IL-12/23-and IFN-gamma-mediated immunity: molecular, cellular, and clinical features. Semin Immunol 18(6):347–361

    Article  CAS  PubMed  Google Scholar 

  16. Yilmaz V, Yentur SP, Saruhan-Direskeneli G (2005) IL-12 and IL-10 polymorphisms and their effects on cytokine production. Cytokine 30(4):188–194

    Article  CAS  PubMed  Google Scholar 

  17. Ma X, Reich RA, Gonzalez O, Pan X, Fothergill AK, Starke JR, Teeter LD, Musser JM, Graviss EA (2003) No evidence for association between the polymorphism in the 3′ untranslated region of interleukin-12B and human susceptibility to tuberculosis. J Infect Dis 188(8):1116–1118

    Article  CAS  PubMed  Google Scholar 

  18. Pacheco AG, Cardoso CC, Moraes MO (2008) IFNG +874 T/A, IL10-1082G/A and TNF-308G/A polymorphisms in association with tuberculosis susceptibility: a meta-analysis study. Hum Genet 123(5):477–484

    Article  CAS  PubMed  Google Scholar 

  19. Rossouw M, Nel HJ, Cooke GS, van Helden PD, Hoal EG (2003) Association between tuberculosis and a polymorphic NFkappaB binding site in the interferon gamma gene. Lancet 361(9372):1871–1872

    Article  CAS  PubMed  Google Scholar 

  20. Wu F, Qu Y, Tang Y, Cao D, Sun P, Xia Z (2008) Lack of association between cytokine gene polymorphisms and silicosis and pulmonary tuberculosis in Chinese iron miners. J Occup Health 50(6):445–454

    Article  CAS  PubMed  Google Scholar 

  21. Ding S, Li L, Zhu X (2008) Polymorphism of the interferon-gamma gene and risk of tuberculosis in a southeastern Chinese population. Hum Immunol 69(2):129–133

    Article  CAS  PubMed  Google Scholar 

  22. Tso HW, Ip WK, Chong WP, Tam CM, Chiang AK, Lau YL (2005) Association of interferon gamma and interleukin 10 genes with tuberculosis in Hong Kong Chinese. Genes Immun 6(4):358–363

    Article  CAS  PubMed  Google Scholar 

  23. Ansari A, Talat N, Jamil B, Hasan Z, Razzaki T, Dawood G, Hussain R (2009) Cytokine gene polymorphisms across tuberculosis clinical spectrum in Pakistani patients. PLoS ONE 4(3):e4778

    Article  PubMed  Google Scholar 

  24. Shibasaki M, Yagi T, Yatsuya H, Okamoto M, Nishikawa M, Baba H, Hashimoto N, Senda K, Kawabe T, Nakashima K, Imaizumi K, Shimokata K, Hasegawa Y (2009) An influence of interferon-gamma gene polymorphisms on treatment response to tuberculosis in Japanese population. J Infect 58(6):467–469

    Article  PubMed  Google Scholar 

  25. Jang SY, Kim MK, Lee KR, Park MS, Kim BC, Cho KH, Lee MC, Kim YS (2009) Gene-to-gene interaction between sodium channel-related genes in determining the risk of antiepileptic drug resistance. J Korean Med Sci 24(1):62–68

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by the Natural Science Foundation of Jiangsu Province (BK2008447).

Author information

Authors and Affiliations

  1. Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China

    J. Wang, S. Tang & H. Shen

Authors
  1. J. Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H. Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J. Wang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, J., Tang, S. & Shen, H. Association of genetic polymorphisms in the IL12-IFNG pathway with susceptibility to and prognosis of pulmonary tuberculosis in a Chinese population. Eur J Clin Microbiol Infect Dis 29, 1291–1295 (2010). https://doi.org/10.1007/s10096-010-0985-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-010-0985-0

Keywords

Search

Navigation