Skip to main content

Advertisement

SpringerLink
Log in

Interleukin-10 and Tumor Necrosis Factor-α Gene Polymorphisms in Tuberculosis

  • Published:
Journal of Clinical Immunology Aims and scope Submit manuscript

Abstract

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is an infectious disease in humans killing nearly three million people and eight million cases annually. The cytokines TNF-α and IL-10 have been implicated in the pathogenesis of TB. Certain single nucleotide polymorphisms within the promoter region of the IL10 and TNF genes have been associated with altered levels of circulating IL10 and TNF- α. We analyzed TNF-α (−308 G/A, −238 G/A, −376 G/A) and IL10 (−1,082 G/A, −819 C/T, −592 C/A) polymorphisms in 128 patients with TB and 80 healthy subjects using by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). A significant association was found between TB and −1,082 G allele (Pc: 0.000, O.R 2.22, 95% CI 1.45–3.41). Significant difference was observed in IL10 GCC and ACC haplotypes distribution between TB and control subjects (Pc: 0.000, O.R 2.22, 95% CI 1.45–3.41; Pc: 0.004, O.R 0.53, 95% CI 0.35–0.81). No statistically significant association was found between IL-10 −819 C/T, TNF-α 308 G/A, −238 G/A, −376 G/A polymorphisms, functional TNFα/IL-10 genotypes and TB. Our findings suggest that IL-10 108 2G/A alleles or haplotypes containing these alleles may influence the Th1/Th2 balance and hence may play a role in TB susceptibility and increase risk of developing disease. This polymorphism may be one of the many genetic factors affecting disease outcome.

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.

Institutional subscriptions

Similar content being viewed by others

References

  1. Raviglione M, Snider D, Kochi A. Global epidemiology of tuberculosis. Mortality and morbidity of a worldwide epidemic. JAMA. 1995;273:220–6.

    Article  PubMed  CAS  Google Scholar 

  2. Sılva CL, Bonato VLD, Lıma KM, Coelho-Castelo AAM, Faccıolı LH, Sartorı A, et al. Cytotoxic T cells and mycobacteria. FEMS Microbiol Lett. 2001;197:11–8.

    Article  PubMed  Google Scholar 

  3. Van Deventer SJH. Cytokine and cytokine receptor polymorphisms in infectious disease. Intensive Care Med. 2000;26:98–102.

    Article  Google Scholar 

  4. De Waal Malefyt R, Abrams J, Bennett B, Figdor CG, de Vries JE. Interleukin 10 (IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med. 1991;174:1209–20.

    Article  PubMed  Google Scholar 

  5. Fiorentino DF, Zlotnik A, Mosmann TR, Howard M, O’Garra A. IL-10 inhibits cytokine production by activated macrophages. J Immunol. 1991;146:3445–51.

    Google Scholar 

  6. Takeshita S, Gage JR, Kishimoto T, Vredevoe DL, Martinez-Maza O. Differential regulation of IL-6 gene transcription and expression by IL-4 and Il-10 in human monocytic cell lines. J Immunol. 1996;156:2591–98.

    PubMed  CAS  Google Scholar 

  7. Knight J. Polymorphisms in tumor necrosis factor and other cytokines as risks for infectious diseases and the septic syndrome. Curr Infect Dis Rep. 2001;3:427–39.

    Article  PubMed  Google Scholar 

  8. Westendorp RG, Langermans JA, Huizinga TW, Elouali AH, Verveij CL, Boomsma DI, et al. Genetic influence on cytokine production and fatal meningococcal disease. Lancet. 1997;349:170–73.

    Article  PubMed  CAS  Google Scholar 

  9. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16:1215.

    Article  PubMed  CAS  Google Scholar 

  10. Perrey C, Turner SJ, Pravica V, Howell WM, Hutchinson IV. ARMS-PCR methodologies to determine IL-10, TNF-α, TNF-β and TGF-β1 gene polymorphisms. Transpl Immunol. 1999;7:127–8.

    Article  PubMed  CAS  Google Scholar 

  11. Richardson A, Sisay-Joof F, Ackerman H, Usen S, Katundu P, Taylor T, et al. Nucleotide diversity of the TNF gene region in an African village. Genes Immun. 2001;2:343–8.

    Article  PubMed  CAS  Google Scholar 

  12. Delgado JC, Baena A, Thim S, Goldfeld AE. Ethnic-specific genetic associations with pulmonary tuberculosis. J Infect Dis. 2002;186:1463–8.

    Article  PubMed  CAS  Google Scholar 

  13. Oh JH, Yang CS, Noh YK, Kweon YM, Jung SS, Son JW, Kong SJ, Yoon J, Lee JS, Kım HJ, Park JK, Jo EK, Song CH. Polymorphisms of interleukin-10 and tumour necrosis factor-α genes are associated with newly diagnosed and recurrent pulmonary tuberculosis. Respirology. 2007;12:594–98.

    Article  PubMed  Google Scholar 

  14. Bellamy R, Ruwende C, Corrah T, McAdam KP, Whittle HC, Hill AV. Assessment of the interleukin 1 gene cluster and other candidate gene polymorphisms in host susceptibility to tuberculosis. Tuber Lung Dis 1998;79:83−9.

    Article  PubMed  CAS  Google Scholar 

  15. Lopez-Maderuelo D, Arnalich F, Serantes R, Gonzalez A, Codocen R, Madero R, Vazquez JJ, Montiel C. Interferon-gamma and interleukin-10 gene polymorphisms in pulmonary tuberculosis. Am J Respir Crit Care Med 2003;167:970−5.

    Article  PubMed  Google Scholar 

  16. Tso HW, Ip WK, Chong WP, Tam CM, Chiang AKS, Lau YL. Association of interferon gamma and interleukin 10 genes with tuberculosis in Hong Kong Chinese. Genes Immun. 2005;6:358–63.

    Article  PubMed  CAS  Google Scholar 

  17. Shın HD, Park BL, Kım YH, Cheong HS, Lee IH, Park SK. Common interleukin 10 polymorphism associated with decreased risk of tuberculosis. Exp Mol Med. 2005;37(2):128–32.

    PubMed  Google Scholar 

  18. Oral HB, Ferah B, Uzaslan EK, Basturk B, Bekar A, Akalın H, Ege E, Ener B, Goral G. Interleukin-10 (IL-10) gene polymorphism as a potential host susceptibility factor in tuberculosis. Cytokine 2006;35:6143–7.

    Article  Google Scholar 

  19. Koss K, Fanning GC, Welsh KI, Jewell DP. Interleukin-10 gene promoter polymorphism in English and Polish healthy controls. Polymerase chain reaction haplotyping using 3′ mismatches in forward and reverse primers. Genes Immun. 2000;1:321–24.

    Article  PubMed  CAS  Google Scholar 

  20. Reynard MP, Turner D, Navarrete CV. Allele frequencies of polymorphisms of the tumor necrosis-alpha, interleukin-10, interferon-gamma and interleukin-2 genes in a North European Caucasoid group from the UK. Eur J Immunogenet. 2000;27:241–9.

    Article  PubMed  CAS  Google Scholar 

  21. Hoffmann SC, Stanley EM, Cox ED, DiMercurio BS, Koziol DE, Harlan DM, et al. Ethnicity greatly influences cytokine gene polymorphism distribution. Am J Transplant. 2002;2:560–7.

    Article  PubMed  CAS  Google Scholar 

  22. Mok CC, Lanchbury JS, Chan DW, Lau SC. Interleukin 10 promoter polymorphisms in southern Chinese patients with systemic lupus erythematosus. Arthritis Rheum. 1998;41:1090–5.

    Article  PubMed  CAS  Google Scholar 

  23. Pyo CW, Hur SS, Kim YK, Choi HB, Hong YS, Kim DW, et al. Polymorphisms of IL-1B, IL-1RN, IL-2, IL-4, IL-6, IL-10, and IFN-γ genes in the Korean population. Hum Immunol. 2003;64:979–89.

    Article  PubMed  CAS  Google Scholar 

  24. Ide A, Kawasaki E, Abiru N, Sun F, Takahashi R, Kuwahara H, et al. Genetic association between interleukin-10 gene promoter region polymorphisms and type I diabetes age-at-onset. Hum Immunol. 2002;63:690–5.

    Article  PubMed  CAS  Google Scholar 

  25. Kroeger KM, Carville KS, Abraham LJ. The −308 tumour necrosis factor-alpha promoter polymorphism effects transcription. Mol Immunol. 1997;34:391–9.

    Article  PubMed  CAS  Google Scholar 

  26. Amirzargar AA, Danesh AA, Khosravi F, Niknam HH, Nikbin B. Cytokines genes polymorphisms in Iranian patients with pulmonary tuberculosis. IJI. 2004;2:125–9.

    Google Scholar 

  27. Henao MI, Montes C, París SC, García LF. Cytokine gene polymorphisms in Colombian patients with different clinical presentations of tuberculosis. Tuberculosis. 2006;86:11–9.

    Article  PubMed  Google Scholar 

  28. Vejbaesya S, Chıerakul N, Luangtrakool P, Sermduangprateep C. NRAMP1 and TNF-α polymorphisms and susceptibility to tuberculosis in Thais. Respirology. 2007;12:202–6.

    Article  PubMed  Google Scholar 

  29. Oliveıra MM, Sılva JCS, Costa JF, Amım LH, Loredo CCS, Melo H, Queıroz LF, et al. Single Nucleotide Polymorphisms (SNPs) of the TNF-a (−238/−308) gene among TB and non TB patients: susceptibility markers of TB occurrence. Jornal Brasileiro de Pneumologia 2004;30:461–67.

    Google Scholar 

  30. Correa PA, Gomez LM, Cadena J, Anaya JM. Autoimmunity and tuberculosis. Opposite association with TNF polymorphism. J Rheumatol. 2005;32:219–24.

    PubMed  Google Scholar 

  31. Hill AVS, Ruwende C, McGuire W, Bellamy R, Coleman E, Ali S, Loke H, Corrah T, Snow R, Marsh K, Greenwood B, McAdam KJWP, Whittle HC, Kwiatkowski D. Association of the TNF −238 promoter polymorphism with susceptibility to tuberculosis and malaria in Africa. Hum Immunol. 1996;47:118.

    Article  Google Scholar 

  32. Lio D, Candore G, Colombo A, Colonna Romano G, Gervasi F, Marino V, Scola L, Caruso C. A genetically determined high setting of TNF-α influences immunological parameters of HLA-B8, DR3 positive subjects: implications for autoimmunity. Hum Immunol. 2001;62:705–13.

    Article  PubMed  CAS  Google Scholar 

  33. Price P, Witt C, Allcock R, Sayer D, Garlepp M, Kok CC, French M, Mallal S, Christiansen F. The genetic basis for the association of the 8.1 ancestral haplotype (A1, B8, DR3) with multiple immunopathological diseases. Immunol Rev. 1999;167:257–74.

    Article  PubMed  CAS  Google Scholar 

  34. Kindler V, Shappino AP, Grau GE, Pignet PF, Vassali P. The inducing role of tumor necrosis factor in the development of bactericidal granulomas during BCG infection. Cell. 1989;56:731–40.

    Article  PubMed  CAS  Google Scholar 

  35. Rojas M, Oliver M, Gros P, Barrera LF, Garcia LF. TNF-a and IL-10 modulate the induction of apoptosis by virulent Mycobacterium tuberculosis in murine macrophages. J Immunol. 1999;162:6122–31.

    PubMed  CAS  Google Scholar 

  36. Gerard C, Bruyns C, Marchant A Abramowicz D, Vandenabeele P, Delvaux A, Fiers W, Goldman M, Velu T. Interleukin-10 reduces the release of tumor necrosis factor and prevents lethality in experimental endotoxaemia. J Exp Med. 1993;177:547–50.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Molecular Biology and Genetics, Science Faculty, Istanbul University, 34118, Vezneciler, Istanbul, Turkey

    Ö. Ates & A. Topal-Sarıkaya

  2. Chest Disease Department, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey

    B. Musellim & G. Ongen

Authors
  1. Ö. Ates
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B. Musellim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G. Ongen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. Topal-Sarıkaya
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ö. Ates.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ates, Ö., Musellim, B., Ongen, G. et al. Interleukin-10 and Tumor Necrosis Factor-α Gene Polymorphisms in Tuberculosis. J Clin Immunol 28, 232–236 (2008). https://doi.org/10.1007/s10875-007-9155-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10875-007-9155-2

Keywords

Search

Navigation