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Association of interferon gamma and interleukin 10 genes with tuberculosis in Hong Kong Chinese

Abstract

Interferon gamma (IFN-γ) and interleukin 10 (IL-10) are believed to play opposing roles in host immunity against mycobacterial infection. IFN-γ activates macrophages, while IL-10 downregulates the expression of T helper type 1 cytokines, MHC class II antigens and costimulatory molecules on macrophages. Associations of IFN-γ −179 (G/T), +874 (A/T), +875 miscrosatellite CA repeats and +4766 (C/T), and IL-10 −1082 (A/G), −819 (C/T) and −592 (C/A) with tuberculosis (TB) were investigated in 385 HIV-negative patients and 451 controls in a Hong Kong Chinese population. The frequency of a low IFN-γ-producing +874 A/A genotype was significantly over-represented in the patient group (P<0.001, OR=3.79, 95% CI=1.93–7.45). We identified 10 alleles in the IFN-γ CA repeats and observed a significant difference in allele frequency distribution between patients and controls (P<0.001). By grouping alleles into 12 and non-12 CA repeats, the non-12/non-12 genotype yielded a similar significant result (P<0.001, OR=4.56, 95% CI=2.21–9.43) as observed in +874 A/A genotype. Weak associations of the IL-10 GCC/− genotype (P=0.04) and the low IFN-γ-producing A/A genotype (P=0.06) with TB relapse/extrapulmonary cases were found. This study suggests the possible role of interferon gamma in TB susceptibility.

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References

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

    Article  CAS  PubMed  Google Scholar 

  2. Collins HL, Kaufmann SH . The many faces of host responses to tuberculosis. Immunology 2001; 103: 1–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Cooper AM, Dalton DK, Stewart TA, Griffin JP, Russell DG, Orme IM . Disseminated tuberculosis in interferon gamma gene-disrupted mice. J Exp Med 1993; 178: 2243–2247.

    Article  CAS  PubMed  Google Scholar 

  4. Casanova JL, Abel L . The human model: a genetic dissection of immunity to infection in natural conditions. Nat Rev Immunol 2004; 4: 55–66.

    Article  CAS  PubMed  Google Scholar 

  5. Pravica V, Perrey C, Stevens A, Lee JH, Hutchinson IV . 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 2000; 61: 863–866.

    Article  CAS  PubMed  Google Scholar 

  6. Bream JH, Ping A, Zhang X, Winkler C, Young HA . A single nucleotide polymorphism in the proximal IFN-gamma promoter alters control of gene transcription. Genes Immun 2002; 3: 165–169.

    Article  CAS  PubMed  Google Scholar 

  7. Bream JH, Carrington M, O'Toole S et al. Polymorphisms of the human IFNG gene noncoding regions. Immunogenetics 2000; 51: 50–58.

    Article  CAS  PubMed  Google Scholar 

  8. Moore KW, de Waal Malefyt R, Coffman RL, O'Garra A . Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 2001; 19: 683–765.

    Article  CAS  PubMed  Google Scholar 

  9. North RJ . Mice incapable of making IL-4 or IL-10 display normal resistance to infection with Mycobacterium tuberculosis. Clin Exp Immunol 1998; 113: 55–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Turner J, Gonzalez-Juarrero M, Ellis DL et al. In vivo IL-10 production reactivates chronic pulmonary tuberculosis in C57BL/6 mice. J Immunol 2002; 169: 6343–6351.

    Article  CAS  PubMed  Google Scholar 

  11. Turner DM, Williams DM, Sankaran D, Lazarus M, Sinnott PJ, Hutchinson IV . An investigation of polymorphism in the interleukin-10 gene promoter. Eur J Immunogenet 1997; 24: 1–8.

    Article  CAS  PubMed  Google Scholar 

  12. Pravica V, Asderakis A, Perrey C, Hajeer A, Sinnott PJ, Hutchinson IV . In vitro production of IFN-gamma correlates with CA repeat polymorphism in the human IFN-gamma gene. Eur J Immunogenet 1999; 26: 1–3.

    Article  CAS  PubMed  Google Scholar 

  13. Torres M, Herrera T, Villareal H, Rich EA, Sada E . Cytokine profiles for peripheral blood lymphocytes from patients with active pulmonary tuberculosis and healthy household contacts in response to the 30-kilodalton antigen of Mycobacterium tuberculosis. Infect Immun 1998; 66: 176–180.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Lopez-Maderuelo D, Arnalich F, Serantes R et al. Interferon-gamma and interleukin-10 gene polymorphisms in pulmonary tuberculosis. Am J Respir Crit Care Med 2003; 167: 970–975.

    Article  PubMed  Google Scholar 

  15. Samten B, Ghosh P, Yi AK et al. Reduced expression of nuclear cyclic adenosine 5′-monophosphate response element-binding proteins and IFN-gamma promoter function in disease due to an intracellular pathogen. J Immunol 2002; 168: 3520–3526.

    Article  CAS  PubMed  Google Scholar 

  16. Lio D, Marino V, Serauto A et al. Genotype frequencies of the +874T → A single nucleotide polymorphism in the first intron of the interferon-gamma gene in a sample of Sicilian patients affected by tuberculosis. Eur J Immunogenet 2002; 29: 371–374.

    Article  CAS  PubMed  Google Scholar 

  17. Rossouw M, Nel HJ, Cooke GS, van Helden PD, Hoal EG . Association between tuberculosis and a polymorphic NFkappaB binding site in the interferon gamma gene. Lancet 2003; 361: 1871–1882.

    Article  CAS  PubMed  Google Scholar 

  18. Lee JY, Goldman D, Piliero LM, Petri M, Sullivan KE . Interferon-gamma polymorphisms in systemic lupus erythematosus. Genes Immun 2001; 2: 254–257.

    Article  CAS  PubMed  Google Scholar 

  19. Stead WW . The origin and erratic global spread of tuberculosis. How the past explains the present and is the key to the future. Clin Chest Med 1997; 18: 65–77.

    Article  CAS  PubMed  Google Scholar 

  20. Delgado JC, Baena A, Thim S, Goldfeld AE . Ethnic-specific genetic associations with pulmonary tuberculosis. J Infect Dis 2002; 186: 1463–1468.

    Article  CAS  PubMed  Google Scholar 

  21. 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. Tuberi Lung Dis 1998; 79: 83–89.

    Article  CAS  Google Scholar 

  22. Pyo CW, Hur SS, Kim YK et al. Polymorphisms of IL-1B, IL-1RN, IL-2, IL-4, IL-6, IL-10, and IFN-gamma genes in the Korean population. Hum Immunol 2003; 64: 979–989.

    Article  CAS  PubMed  Google Scholar 

  23. Ide A, Kawasaki E, Abiru N et al. Genetic association between interleukin-10 gene promoter region polymorphisms and type 1 diabetes age-at-onset. Hum Immunol 2002; 63: 690–695.

    Article  CAS  PubMed  Google Scholar 

  24. Chong WP, Ip WK, Wong WH, Lau CS, Chan TM, Lau YL . Association of interleukin-10 promoter polymorphisms with systemic lupus erythematosus. Genes Immun 2004; 5: 484–492.

    Article  CAS  PubMed  Google Scholar 

  25. Gibson AW, Edberg JC, Wu J, Westendorp RG, Huizinga TW, Kimberly RP . Novel single nucleotide polymorphisms in the distal IL-10 promoter affect IL-10 production and enhance the risk of systemic lupus erythematosus. J Immunol 2001; 166: 3915–3922.

    Article  CAS  PubMed  Google Scholar 

  26. Tso HW, Lau YL, Tam CM, Wong HS, Chiang AK . Associations between IL12B polymorphisms and tuberculosis in the Hong Kong Chinese population. J Infect Dis 2004; 190: 913–919.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank HS Wong for assistance in statistical analyses. This study was funded by The Outstanding Researcher Award of the University of Hong Kong (YL Lau), Edward Sai Kim Ho Tung Paediatric Education and Research Fund (HW Tso), the Shun Tak District Min Yuen Tong and the Genome Research Centre of the University of Hong Kong.

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Correspondence to Y L Lau.

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Tso, H., Ip, W., Chong, W. et al. Association of interferon gamma and interleukin 10 genes with tuberculosis in Hong Kong Chinese. Genes Immun 6, 358–363 (2005). https://doi.org/10.1038/sj.gene.6364189

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